The effect of tobacco smoking on alprazolam [a sedative-hypnotic] pharmacokinetics is investigated. Healthy men (5 smokers adn 5 nonsmokers) 19-42 yr old received a single oral 1 mg alprazolam dose followed 48 h later by alprazolam 0.5 mg every 8 h for 6 days. Multiple serum samples were collected following the initial dose and after the last 0.5 mg dose and analyzed by GLC for alprazolam. Pharmacokinetic values were calculated, and mean data from the smoking and nonsmoking groups were compared. Mean plasma alprazolam concentrations during the single-dose phase were comparable between groups. During the multiple-dose phase, mean plasma concentrations were 15-30% lower in the smokers. Total body clearance of alprazolam was 24% greater and the apparent volume of distribution was 17% less in smokers. The elimination half-life was 49% greater in nonsmokers. These differences were not significant. Changes were not observed in elimination half-life or clearance after alprazolam cessation. Steady-state pharmacokinetic values during the multiple-dose phase correlated with values observed following the single dose. Although not significantly different, alprazolam elimination was more rapid in smokers than in non-smokers.