A double-blind comparative study of doxazosin and prazosin when administered with beta-blockers or diuretics. The antihypertensive efficacy and safety of doxazosin (once daily) and prazosin (twice daily) were compared in patients with mild or moderate essential hypertension (diastolic blood pressure [DBP] 95 to 114 mm Hg) not adequately controlled by diuretics and beta-blockers. Doxazosin produced significantly greater mean reductions in standing (p = 0.01) and supine (p = 0.04) DBP than did prazosin; there were no significant between-group differences in either mean systolic blood pressure or heart rate. The overall mean daily doses for efficacy-evaluable patients were 4.7 mg of doxazosin and 6.7 mg of prazosin. Sixteen patients (84.2%) treated with doxazosin and 13 patients (56.5%) treated with prazosin were considered therapeutic successes (decrease in standing DBP greater than or equal to 10 mm Hg or to less than or equal to 90 mm Hg with greater than or equal to 5 mm Hg reduction from baseline). Of the 19 efficacy-evaluable patients treated with doxazosin, 15 (78.9%) showed improvement in the severity category of hypertension; an improvement in severity was reported in 14 patients (60.9%) treated with prazosin. Doxazosin produced a more favorable effect on serum lipid levels than did prazosin, although no statistically significant within- or between-group differences were observed. Most side effects experienced with either doxazosin or prazosin were mild or moderate and were tolerated or disappeared with continued treatment. The overall evaluation of toleration was excellent or good for 18 (90%) doxazosin- and 21 (91%) prazosin-treated patients. Clinical efficacy was rated as excellent or good for 16 patients (80%) treated with doxazosin and 15 patients (68%) treated with prazosin. 