Labetalol 1-5 mg/kg administered intravenously to normal subjects in the supine position produced an immediate mean fall in systolic (16%) and diastolic (25%) blood pressure with a concomitant increase in heart rate (12%). After graded exercise, intravenous labetalol inhibited increases in heart rate and blood pressure. Isoprenaline log dose response curves of increase in heart rate and reduction in diastolic pressure after intravenous labetalol shifted to the right in a parallel manner compared with pre-labetalol response curves suggestive of competitive antagonism at beta-adrenoceptor sites. Similarly, phenylephrine dose response curves of increase in systolic pressure before and after intravenous labetalol were suggestive of competitive antagonism at alpha-adrenoceptor sites. The ratio of relative potency alpha: beta adrenoceptor antagonism after intravenous labetalol was approximately 1:7, whereas in the same subjects after oral labetalol the ratio was approximately 1:3 as previously reported. Using the inhibition of isoprenaline tachycardia to estimate the potency of the beta-adrenoceptor antagonism of labetalol relative to that of propranolol the potency ratio was 1:6. However, using inhibition of Valsalva tachycardia as the index, the estimated ratio was approximately 1:3. Estimates of relative potency using inhibition of tilt tachycardia were complicated by the additional effects upon blood pressure after labetalol not seen after propranolol. Labetalol produced adrenoceptor blockade at both alpha and beta sites in man sufficient to explain its therapeutic antihypertensive effect.