The effect of age and gender on the stereoselective pharmacokinetics of propranolol was studied in 12 young (25 to 33 years old) and 12 elderly (62 to 79 years old) healthy nonsmoking volunteers, half of whom were female. Racemic propranolol was administered (80 mg p.o.) each 8 hr for seven doses. Serum was obtained just before (0 time) and at 0.5, 1, 2, 4, 6, 8, 10, 12 and 24 hr after the final dose and analyzed for propranolol enantiomers. The serum concentration of alpha-1 acid glycoprotein was determined before propranolol administration. The binding of each enantiomer to serum proteins was determined in samples obtained before propranolol administration and two hr after the final dose of propranolol. We found that the intrinsic hepatic clearance of S-propranolol was about 30% smaller in the elderly than in the young, whether it was calculated for total or unbound drug. Additionally, the elimination half-lives of both enantiomers were 2- to 3-fold prolonged in the elderly compared with the young. In all subjects regardless of age or sex the intrinsic hepatic clearance of the total (bound plus free) S-isomer was smaller than that of the R-isomer. There was no age-related difference in alpha-1 acid glycoprotein concentration or protein binding of either enantiomer of propranolol. However, there was a gender-related difference with the females having significantly greater binding of the S-enantiomer than the males.(ABSTRACT TRUNCATED AT 250 WORDS)