The correlation between the plasma concentration of prazosin and the effects on supine and standing systemic blood pressure and heart rate was examined at 1/2, 1, 2, 4, and 8 hr after single oral doses of 0.5, 1, 2, and 4 mg in 8 patients with severe refractory heart failure due to coronary heart disease. Despite wide between-patient and within-patient variation in the plasma concentration, the grouped results showed a significant linear relationship between dose, peak concentration, and area under the time-concentration curve. Time of maximum plasma concentration (2 hr) and half-life in plasma (5.6 hr) were similar after all four doses. Compared to the reported pharmacokinetic profile of the drug in normal subjects, the plasma clearance of the drug in these patients in heart failure was substantially reduced. In the recumbent posture there were reductions in systolic and diastolic blood pressure without consistent changes in heart rate after all doses of prazosin. A clear dose-response effect of the drug on both variables only became apparent during standing, when there was a significant correlation between dose, the postural fall in systolic and diastolic blood pressure, and the increase in heart rate. Three of the 8 patients were unable to tolerate more than 1 mg prazosin due to postural hypotension.