The efficacy and tolerability of the alpha-blocker prazosin was compared with that of atenolol, a beta-blocker, in the long-term treatment of uncomplicated, essential hypertension. Twelve patients were randomly assigned to prazosin treatment and 15 to treatment with atenolol. Drug therapy was titrated to reduce diastolic blood pressure by 10 mm Hg or to below 89 mm Hg, whichever was lower. If monotherapy with either study drug failed to do this, hydrochlorothiazide was added to the regimen. Once blood pressure control was established, patients received maintenance therapy at that dosage and were followed for up to 12 months. Blood pressure, side effects, and plasma lipid levels were monitored during this period. Seventy-five percent of patients receiving prazosin monotherapy attained blood pressure goals, compared with 60 percent of patients given atenolol monotherapy. With the addition of low-dose hydrochlorothiazide, those patients not having an adequate response to monotherapy attained blood pressure control. Blood pressure reductions were maintained without dosage adjustment throughout the maintenance period; patient acceptance was good, and there was no evidence of tolerance. Treatment with atenolol produced slight increases in plasma triglyceride levels and little change in total or low-density lipoprotein cholesterol. In contrast, patients treated with prazosin demonstrated no adverse effects with regard to lipid levels. Although a higher percentage of patients reached goal blood pressure with prazosin monotherapy than with atenolol, the response rates were comparable when hydrochlorothiazide was added to the regimens.