Comparison of the hemodynamic and hormonal effects of beta-adrenoceptor antagonists with different ancillary properties may help to clarify the antihypertensive mechanism of these drugs. Under strict basal conditions, the effects of acebutolol (400 mg b.i.d.), atenolol (100 mg b.i.d.), pindolol (10 mg b.i.d.), and propranolol (80 mg t.i.d.), were studied for the first 24 hours in 40 hypertensive patients. With pindolol, mean arterial pressure was reduced (p less than 0.05) 1 hour after administration, whereas the cardiac index and the systemic vascular resistance index did not change. With the other three drugs, the fall in mean arterial pressure was delayed 2-3 hours. With these drugs, the fall in mean arterial pressure was preceded by a rise in the resistance index, which compensated for the initial fall in cardiac index. With each drug, the decrements in mean arterial pressure were associated with parallel decrements in the resistance index, and percent changes in mean arterial pressure and the resistance index were always significantly (p less than 0.001) correlated. At the end of the 24-hour period, the four drugs shared an equal antihypertensive effect, which varied 14-17%. This was associated with a return of the cardiac index toward control values by acebutolol, atenolol, and propranolol treatment and a moderately increased cardiac index above pretreatment values (13%, p less than 0.01) with pindolol. The secondary rise in the cardiac index was inversely correlated (p less than 0.001) with the fall in mean arterial pressure with all four drugs. Plasma renin was maximally suppressed 2 hours after treatment, thus before any change in mean arterial pressure had occurred with acebutolol, atenolol, and propranolol. Pretreatment values of active renin and the reduction of mean arterial pressure 24 hours after administration were not correlated in any of the four groups. Despite the "vasodilator" action of the four drugs, plasma norepinephrine did not rise. Our data show that the main hemodynamic change that occurs at the time blood pressure falls after beta-adrenoceptor antagonism is vasodilation. Neither autoregulation of blood flow nor renin suppression can explain this vasodilator action. The absence of an increase in norepinephrine, despite vasodilation, suggests that beta-adrenoceptor antagonism interferes with sympathetic vasoconstrictor nerve activity. This effect may explain the vasodilator and antihypertensive potential of beta-adrenoceptor antagonists.