To determine if food reduces the hemodynamic and humoral effects of captopril in patients with essential hypertension, we performed two studies. In the acute study, 15 inpatients with uncomplicated essential hypertension randomly received a single oral dose of placebo or captopril (25 mg) while fasting or after eating, or captopril (50 mg) after eating. Blood pressure and heart rate were measured every 30 min up to 4 h (and up to 10 h in six out of the 15 patients), while plasma renin activity, plasma aldosterone, and serum angiotensin-converting enzyme were measured 2 h after dosing. Compared with placebo, captopril significantly reduced mean blood pressure (p less than 0.001), serum angiotensin-converting enzyme (p less than 0.005), and aldosterone (p less than 0.001), increased plasma renin activity (p less than 0.05), and did not change heart rate; there was no difference between the fasting and the fed state. In the six patients followed up to 10 h, captopril both before and after food significantly and similarly reduced mean blood pressure up to 8 h (p less than or equal to 0.05). In the chronic study, 10 patients with uncomplicated essential hypertension, while having prolonged (3-12 months) treatment with captopril (50 mg twice a day), were asked to take captopril for 1 month 1 h before eating and for another month during or immediately after eating. The sequence was randomized, and blood pressure, heart rate, plasma renin activity, serum angiotensin-converting enzyme, and plasma aldosterone were measured at the end of each period 12 h after last dosing.(ABSTRACT TRUNCATED AT 250 WORDS)