Ingestion of alcohol acutely decreases vascular resistance and blood pressure (BP) with activation of the sympathetic nervous system in Orientals. Although α 1-blockers are widely used in the treatment of hypertension, the possible interaction between alcohol and α 1-blockers has not been clarified. We examined the effects of prazosin on the alcohol-induced BP changes in Japanese men with mild hypertension. Ten hypertensive patients (54 ± 3 years, mean ± SE) were given 1 mL/kg of alcohol or isocaloric control drink with a light meal in the evening before and 5 to 7 days after treatment with prazosin (1 mg three times daily). Ambulatory BP monitoring was carried out every 30 min for 24 h in each period using Colin ABPM-630. Blood samples were obtained before and 2 h after intake of alcohol or control drink. Before prazosin treatment, alcohol ingestion decreased BP for several hours with a significant reduction in average 24-h BP, whereas it increased heart rate, plasma norepinephrine, and plasma renin activity. Treatment with prazosin caused a significant decrease in 24-h BP (136.3 ± 4.0/82.8 ± 2.5 v 131.6 ± 3.2/80.0 ± 2.3 mm Hg). The alcohol-induced hypotension at 2–4 h after ingestion was enhanced by prazosin ( −18.0 ± 3.7/ −11.8 ± 2.7 v −24.4 ± 4.9/ −17.8 ± 2.8 mm Hg, P < .05 for diastolic BP). These results suggested that inhibition of the sympathetic nervous system with α 1-blockers accentuates alcohol-induced hypotension. Ingestion of alcohol may cause a marked BP reduction in hypertensive Orientals treated with α 1-blockers.