In a double-blind placebo cross-over study, the beta-blocking potencies of acebutolol and propranolol were compared in ten healthy subjects under steady-state conditions of oral drug administration. Beta-adrenergic blockade, determined by the degree of attenuation of tachycardia induced by standardized multistage treadmill exercise, was correlated with dose as well as with the plasma levels of the two beta antagonists. On a weight-for-weight basis, propranolol was about 4 times as potent as acebutolol in inhibiting exercise-induced tachycardia and in reducing the heart rate times systolic blood pressure product due to exercise. A weak correlation was demonstrated between the degree of beta blockade and plasma concentrations of propranolol (r = 0.381, p less than 0.01) or acebutolol (r = 0.333, p less than 0.001), there being up to 20-24 fold interindividual variation in plasma level for a given dose of each compound. Plasma acebutolol levels were associated with at least twofold greater levels of its acetyl homologue metabolite. A positive linear correlation was found between percentage beta blockade and the corresponding doses of propranolol (r = 0.503, p less than 0.001) and of acebutolol (r = 0.574, p less than 0.001). Our overall data provide little support for the use of plasma levels of acebutolol and propranolol as a guide to beta-blocking therapy with these compounds.