We compared the antihypertensive activity of DL- and D-nebivolol in patients with essential hypertension on clinic and 24-h ambulatory blood pressure (BP) and during dynamic exercise as well. After a 4-week placebo run-in period, 30 patients (mean age 48 years) were randomly allocated to double-blind treatment with either DL-nebivolol 5 mg or D-nebivolol 2.5 mg once daily for 4 weeks. After an interim single-blind placebo washout of 2-4 weeks, all patients crossed over double-blind to the alternative DL- or D-nebivolol treatment for 4 weeks. The results show that DL- and D-nebivolol produced similar reductions in clinic trough (delta systolic/delta diastolic BP (delta SBP/delta DBP): -10/-8 and -13/-9 mm Hg, respectively, all p < 0.0001 vs. placebo), 24-h ambulatory (-12/-11 and -13/-11 mm Hg, respectively, all p < 0.0001), and peak exercise BP (-13/-6, both p < 0.01; and -13/-7 mm Hg, both p < 0.0001, respectively) as compared with placebo (SBP/DBP clinic 147/99, ambulatory 147/94, exercise 211/103 mm Hg). Our results showing superimposable clinic and ambulatory BP profiles as well as exercise BP responses with DL- and D-nebivolol treatment do not confirm results of animal pharmacologic experiments in which the L-isomer potentiated the antihypertensive effect of the D-isomer.