When D,L-propranolol, 100 mg/kg/day, was added to the drinking water of spontaneously hypertensive rats (SHR), systolic pressures measured with the tail-cuff method fell significantly within 1 month and were almost the same as those in normotensive controls (KNR) by the end of 3 months. This antihypertensive effect was later confirmed by direct recording of phasic aortic pressures from indwelling catheters. Blood pressure was lowered selectively only in SHR and not in KNR; by contrast, body weight, fluid intake, and heart rate always decreased whether the rats were hypertensive or not. Because pressor responses to hypothalamic stimulation in SHR treated with propranolol were reduced while those to injected norepinephrine were unaltered, a peripheral inhibition of cardiovascular reactivity was considered unlikely. Supporting the interpretation that diminished pressor responsiveness was caused by concurrent reduction of sympathetic vasomotor activity, frequency of spike potentials recorded from abdominal sympathetic nerves was appreciably lessened in propranolol-treated SHR, as was the vasodepression resulting when autonomic ganglia were pharmacologically blocked with pentolinium. These findings are consistent with the conclusion that prolonged oral administration of propranolol prevents development of spontaneous hypertension in rats by reducing sympathetic vasomotor tons.