Sixteen normal healthy female volunteers, ages 22 to 42 years, participated in this study to determine the pharmacokinetic characteristics of zolpidem and the influence of oral contraceptives and smoking. Five of the volunteers were cigarette smokers, and 8 were on oral contraceptive preparations (OCP). All subjects received a 5 mg oral dose of zolpidem tartrate, followed by multiple blood samples that were assayed by HPLC with fluorescence detection. Among all subjects, mean apparent oral clearance was 376 ml/min (5.8 ml/min/kg), elimination half-life was 2.4 hours, and maximum serum zolpidem concentration was 60 ng/ml. Clearance was higher (445 vs. 345 ml/min) and half-life was shorter (1.8 vs. 2.7 h) in smokers than nonsmokers, although the differences were not statistically significant. Likewise, zolpidem clearance was higher and half-life shorter in women using OCP but differences were not significant. Differences in zolpidem kinetics associated with smoking may be explained by the small contribution of cytochrome P450-1A2 to net clearance of zolpidem. In any case, the differences were quantitatively small and not likely to be of clinical importance.