1. Blood pressure, systemic haemodynamics, plasma volume, renin and aldosterone were measured during placebo treatment and after 1, 4 and 12 weeks of hydrochlorothiazide in 13 patients with uncomplicated essential hypertension. Nine of these patients were also studied after 24 and 36 weeks of treatment.
2. Mean arterial pressure was lowered significantly during hydrochlorothiazide treatment. In seven patients the fall in mean arterial pressure was greater than 10% (responders); four of these were studied for 36 weeks. The remainder were considered non-responders.
3. Hydrochlorothiazide lowered cardiac output. The maximal decrease was observed after 12 weeks of treatment (P < 0·01). In responders this was followed by a return to pretreatment values and a significant decrease in total peripheral resistance, whereas in non-responders cardiac output remained reduced and total peripheral resistance was permanently elevated.
4. Changes in plasma volume, renin and aldosterone were not significantly different in responders and non-responders although non-responders tended to show a greater degree of plasma volume depletion and a more pronounced increase in plasma aldosterone.
5. Thus it is unlikely that the initial decrease in cardiac output is an important determinant of the long-term haemodynamic effect of thiazide diuretics.