Hypertension and diabetes mellitus frequently coexist and are independent risk factors for reduced peripheral perfusion. Antihypertensive medications that reduce blood pressure and improve peripheral perfusion would have advantages in diabetic hypertensive patients. In a randomized, two-placebo-period, single-blind, two-way, crossover study, finger and forearm blood flow, lipid levels, and blood pressure control were determined in 19 diabetic hypertensive patients given prazosin and atenolol, with each drug and placebo period lasting four weeks. Both drugs reduced blood pressure (sitting, 157/95 to 142/84 mm Hg for atenolol and 155/95 to 138/82 mm Hg for prazosin; standing, 154/94 to 144/84 mm Hg for atenolol and 154/94 to 133/81 mm Hg for prazosin). Lipid levels did not change, except that low-density lipoprotein levels decreased from 148 to 127 mg/dl with prazosin. Atenolol did not change forearm or finger blood flow or vascular resistance. Prazosin increased blood flow and reduced vascular resistance in both finger and forearm. In conclusion, prazosin demonstrated a potentially more appropriate hemodynamic profile than atenolol in diabetic hypertensive patients in this study.