We wished to assess the effects of beta-blockade on baroreflex sensitivity and standard tests of integrity of autonomic nervous function in patients with coronary artery disease, and to determine whether the effects of lipophilic (metoprolol) and hydrophilic (atenolol) beta-blockers differ. Beta-blocking drugs increase spontaneous heart rate variability in healthy subjects and in patients with coronary heart disease, but little is known about their effects on baroreflex sensitivity and heart-rate based tests of autonomic integrity. In a randomly allocated double-blind crossover study with three 2-week treatment periods, metoprolol CR 200 mg once a day, or atenolol 100 mg once a day, or placebo once a day, were administered to 18 male patients with stable coronary artery disease. Baroreflex sensitivity was determined from the natural baroreflex challenge of Valsalva strain. Heart rate reactions to standard stimuli were measured. No significant differences were found between the effects of atenolol and metoprolol. Beta-blockade did not significantly affect the baroreflex sensitivity, but it diminished the Valsalva ratio significantly (P < 0.001). The difference between maximum and minimum heart rate during hyperventilation was also significantly lower during beta-blockade. The heart rate response to standing up and the ratio of maximum to minimum heart rate during deep breathing were not influenced by beta-blockade. Discontinuation of beta-blockade seems to be unnecessary for reliable determination of baroreflex sensitivity in patients with coronary artery disease, when the natural pressure challenge of Valsalva strain is sued. Both hydrophilic and lipophilic bet-blockers interfere with certain diagnostic tests of autonomic nervous function.(ABSTRACT TRUNCATED AT 250 WORDS)