1. Incomplete mixing of alveolar gas may be expressed as an equivalent alveolar dead space serving a remaining alveolar space in which mixing is regarded as complete. Calculation of this dead space during multiple-breath, inert gas wash-in or wash-out leads to an estimate of ‘multiple-breath alveolar mixing efficiency’ (MBME). 2. We measured MBME in 25 healthy subjects and six patients with chronic airflow limitation (CAL), and in three asthmatic patients before and after bronchial provocation with histamine aerosol, from successive breaths during open-circuit, multiple-breath wash-in of a mixture containing helium (He) and sulphur hexafluoride (SF 6 ). The simultaneous use of a light and a heavy gas helps to identify diffusive mechanisms. 3. MBME fell almost linearly with log Z , the proportion of total wash-in remaining uncompleted. For a given Z , MBME was always lower for SF 6 than for He in the same subject. In health the lowest MBME (52.2%) was seen for SF 6 in a man aged 21 years. The same wash-in yielded a ventilation distribution with an extreme range of specific ventilation of less than 1 decade. MBME of this order is thus consistent with estimates of ventilation distribution in health. 4. Patients with CAL showed a big increase in the volume of the conducting airways or ‘series dead space’ ( V D S) for both gases, and V D S was always bigger for SF 6 than for He. This very large V D S appears to be the main reason for wash-in delay in these patients, followed by impaired diffusive mixing in the peripheral air spaces. Ventilation maldistribution may play little part in the mixing defect. 5. In asthma, bronchoconstriction by histamine reduced V D S and MBME, but MBME did not differ between He and SF 6 . This suggests a shortening of diffusion distances beyond the narrowed bronchioles which may help to mitigate the (here predominant) effects of maldistribution on mixing efficiency.

1. Physiological dead-space volume ( V D ) was measured in twenty-four healthy men and women aged from 20 to 71 years, at rest and at two rates of work on a treadmill, whilst breathing air and breathing oxygen. 2. The effect of correction of arterial carbon dioxide tension ( P a,co 2 ) to pulmonary capillary temperature on the resulting value for V D was investigated. We find that the effect is substantial and that a correction should be made. 3. Equations have been derived for the prediction of normal V D during exercise. The best prediction was given by a regression on height, age, carbon dioxide output, ventilation and respiratory frequency, with an upper 95% confidence limit of +81 ml.

1. Venous admixture/cardiac output ratio (Q̇va/Q̇t) has been measured in twenty-four healthy volunteer subjects of both sexes aged 20–71 years, at rest and during the steady state of treadmill exercise at two rates of work, and breathing air and breathing oxygen. 2. With oxygen breathing, Q̇va/Q̇t was considerably less during exercise than during the time subjects were taking either normal or deep breaths of oxygen at rest, and did not significantly increase with the intensity of exercise. It is postulated that the increase in ventilation during exercise opens most or all of those alveoli which, during oxygen breathing at rest, close because of critically low ventilation/perfusion (V̇/Q̇) ratios. 3. With air breathing, Q̇va/Q̇t fell from rest to exercise (especially in older subjects), presumably due to improved ventilation of alveoli at the lung bases. With an increase in work rate Q̇va/Q̇t increased in all age groups. This increase was not due to increase in the shunt fraction (Q̇ s /Q̇t), nor to limitation of diffusing capacity; it arose from an increase in V̇/Q̇ variance. 4. Equations have been derived for the prediction of normal Q̇va/Q̇t during exercise, with or without correction for the effects of increasing pulmonary capillary temperature. These effects do not materially influence the accuracy of prediction, but may be relevant to some of the interpretations. In particular, they provide a further indication that Q̇s/Q̇t probably cannot be measured by breathing oxygen at rest, even in deep breathing.

1. The alveolar-arterial oxygen-tension gradient was measured in duplicate, in forty-eight healthy subjects (twenty-four men and twenty-four women) aged from 20 to 74 years, while breathing oxygen concentrations of approximately 14, 21, 40, 60 and 100%. 2. The gradient increased with age and with inspired O 2 concentration up to 60%. Above 60%, during normal breathing, there was no significant change in gradient. 3. Breathing 100% O 2 in deep breaths decreased the gradient in all age-groups, significantly so in subjects of 50 years and younger. The remaining gradient was due to anatomical venous shunt. 4. When this anatomical shunt was allowed for, the differences in gradient between age-groups were largely abolished at all inspired O 2 concentrations. The gradient which was not due to anatomical shunt, when breathing air, remained higher in subjects over 60 years than in the younger subjects. 5. The results can be interpreted to mean that three components contribute to the normal gradient: (a) irreversible anatomical shunt; (b) closed, unventilated alveoli which can only be inflated by deep breaths; and (c) cyclical airway closure during normal breathing in subjects over 60 years. Diffusion disequilibrium may contribute a gradient of up to 3 mmHg during the breathing of low O 2 concentrations.

1. Two-hundred and forty duplicate estimations of physiological dead-space volume ( V D ) were made in forty-eight healthy subjects (twenty-four men and twenty-four women) aged from 20 to 74 years, to assess the predictive accuracy of various standards. 2. The V D / V T (physiological dead-space volume/tidal volume) ratio standard was least precise, but could be improved by allowing for sex and age. 3. The best prediction could be made by multiple regression of V D on age, height, tidal volume ( V T ) and the reciprocal of respiratory frequency (f), which gave an estimate with a standard deviation of 24·7 ml. 4. Theoretical and practical arguments favour the abandonment of the V D / V T ratio standard. Simple regression of V D on V T also is unsatisfactory, giving a much less precise estimate of V D than a multiple regression on V T and other variables.