1. Pulmonary function tests, including alveolar mixing efficiency by the single-breath and multi-breath methods, and ventilation scans were performed on 16 volunteer subjects. The tests were repeated after the inhalation of a methacholine aerosol in sufficient dosage to increase airways resistance.

2. After inhalation of methacholine there was a significant fall in mean series dead space of 31 ml (P < 0.05), and mean multi-breath alveolar mixing efficiency fell from 68% to 36% (P < 0.001), a fall occurring in all subjects. Mean single-breath alveolar mixing efficiency measured on the first breath of the nitrogen washout fell from 76% to 70%, but this change did not reach statistical significance (0.1 > P > 0.05).

3. In eight of the subjects, technically adequate lung scans and pulmonary function tests were obtained both before and not more than 30 min after methacholine inhalation. In seven there were obvious visible defects on the ventilation scans, and in five of these the computer-calculated underventilation score became abnormal.

4. Thus inhalation of methacholine causes maldistribution of ventilation, a fall in alveolar mixing efficiency and a fall in series dead space, presumably brought about by bronchoconstriction. The parallel component of this maldistribution of ventilation, as judged by 81mKr ventilation scanning, does not of itself seem to be sufficient to explain the fall in alveolar mixing efficiency, and therefore a degree of diffusion limitation is probably involved as well.

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