In an observer-blind four-way crossover study, 7 healthy volunteers received in random sequence, one month apart, atenolol 100 mg od, propranolol (slow release) 160 mg od, pindolol 5 mg tid, and nebivolol 5 mg od for a period of seven days, followed by a single-blind placebo washout period of seven days. The decrease of peak exercise heart rate and systolic blood pressure was significant (p = 0.02) and comparable for the four drugs studied and varied between 15% and 23% for heart rate and between 15% and 20% for systolic blood pressure. Although no statistically significant difference was observed among the four drug regimens, the decrease of peak exercise heart rate was less pronounced with nebivolol than with the three reference beta-blocking agents. The ratio of the preejection period (PEPc) to the left ventricular ejection time (LVETc), an indirect measure of left ventricular performance, tended to increase with atenolol and propranolol and remained unchanged with pindolol. PEPc/LVETc progressively and significantly improved with nebivolol from a control value of 0.37 +/- 0.012 to 0.31 +/- 0.009 (p = 0.03) after seven days of treatment, owing to a decrease in PEPc and an increase in LVETc, suggestive of a combined effect both on preload and afterload. Postexercise LVETc, an index of the intrinsic positive inotropy of exercise, was significantly suppressed by atenolol, propranolol, and pindolol, but not during treating with nebivolol. These data suggest that nebivolol is a beta 1-selective adrenergic antagonist with an unusual hemodynamic profile, probably improving left ventricular compliance.