Intravenous hydralazine, 0.15, 0.30 or 0.60 mg/kg, was administered to 11 supine hypertensives on two occasions: once after pretreatment with intravenous propranolol, 0.1 mg/kg, and once after pretreatment with intravenous placebo. The average fall in mean arterial pressure for each dosage of hydralazine was no different with or without propranolol, even though propranolol inhibited rises in plasma renin activity and pulse due to hydralazine. However, in each of four patients who had high supine baseline plasma renin activity, propranolol enhanced the fall in blood pressure caused by hydralazine. A second group of patients was given an infusion of 0.01 or 0.02 mg/kg per minute phentolamine, which did not change baseline blood pressure. Subsequent administration of intravenous hydralazine, 0.15 mg/kg, resulted in a fall in blood pressure which was larger than previously observed with intravenous hydralazine alone, regardless of supine baseline plasma renin activity. These data are consistent with the hypothesis that reflex catecholamine release interferes with the hypotensive effect of intravenous hydralazine. Pretreating with propranolol weakens homeostatic defenses against hydralazine such as rises in pulse rate and plasma renin activity. However, propranolol appears to enhance the alpha-adrenergic effect of released catecholamines, and the antihypertensive response to hydralazine is unaltered. In patients with high supine plasma renin activity, propranolol potentiates the fall in blood pressure induced by hydralazine, perhaps because the hypertension in such patients is renin dependent.