The mechanism of action of prazosin hydrochloride, a new antihypertensive agent was studied in 14 patients with essential hypertension. Mean supine blood pressure for the group fell from 148/102 +/- 3/2 (SE) mm Hg at baseline to 139/91 +/- 5/4 after eight weeks of therapy (P less than 0.05). No significant postural hypotension was noted in the patients who responded to therapy. Glomerular filtration rate (endogenous creatinine or inulin clearance) and effective renal plasma flow (PAH clearance) remained unchanged during therapy as did supine and stimulated peripheral plasma renin activity. Cardiac output did not change significantly although plasma volume increased in ten out of 12 patients in whom it was measured (P less than 0.025). Among the patients whose mean blood pressure fell 10 mm Hg or more, peripheral vascular resistance fell significantly (P less than 0.025), and the change in plasma volume was not statistically significant. Among the patients whose mean blood pressure changed less than 10 mm Hg with therapy, there was no significant change in peripheral vascular resistance and plasma volume increased significantly (P less than 0.025). Prazosin hydrochloride appears to be an effective antihypertensive agent which acts by peripheral vasodilatation. It may cause fluid retention. The drug does not appear to affect renal function or renin secretion.