Most alpha-receptor blocking drugs require divided daily administration because of a short plasma half-life. This multicenter study examined the effectiveness and safety of once-daily administration with doxazosin, a quinazoline analog alpha 1-receptor blocking drug with a plasma half-life of 19 hours. Patients with diastolic blood pressure (BP) of 90 to 115 mm Hg entered 4 weeks of single-blind placebo therapy and then were randomized to double-blind treatment with doxazosin (63 patients) or placebo (67 patients). After 10 weeks of titration, standing arterial BP was lowered by 14/11 mm Hg with doxazosin and by 0.5/0.9 mm Hg with placebo (p less than 0.001). Measured hourly for 12 hours after the dose, all standing and supine arterial BP values were significantly lower in the doxazosin group at each hour. Pulse rate increased slightly in both groups int he double-blind phase, but the increase with doxazosin never significantly exceeded that of placebo. Dizziness was the most common complaint with doxazosin, but syncope did not occur. Side effects were mild and transient and did not necessitate withdrawing any participants from the study. Body weight increased by 1.5 kg in the doxazosin group and decreased by 0.2 kg in the placebo group (p less than 0.01). Safe and effective in once-daily administration, doxazosin is suitable for initial therapy in mild and moderate hypertension.