In this clinical investigation, four groups of subjects (eight young women and eight young men [age range, 18 to 25 years], and eight elderly women and eight elderly men [greater than 60 years of age]) received single oral doses (400 mg) of racemic mephobarbital. The apparent total body clearance of R-mephobarbital was much greater and the elimination half-life was much shorter in the young men compared with the other three groups. This enantiomer displayed an age-dependent gender effect and a gender-dependent age effect in its metabolism. The apparent total body clearance of the S-enantiomer was much lower than that of the R-enantiomer in all subjects and did not differ between subject groups, although the elimination half-life was slightly but significantly shorter in young males. A consequence of these enantiomeric differences was an apparently enhanced stereoselectivity in the metabolism of mephobarbital in young men. These substantial influences of age and gender on the stereoselective disposition of mephobarbital are consistent with recent findings concerning the expression and regulation of cytochrome P450 enzymes.