This study was undertaken to determine whether there are pharmacokinetic (PK) interactions between zolpidem, a hypnotic, and sertraline, an antidepressant. Twenty-eight healthy female volunteers received a single dose of zolpidem alone and five consecutive dose(s) of zolpidem 10 mg in the presence of chronic doses (19 days) of sertraline 50 mg. Using HPLC, plasma levels of zolpidem, sertraline, and N-desmethylsertraline were determined at different times throughout the study and PK parameters derived. Compared to zolpidem alone, the T 1/2 of the first dose of zolpidem in the presence of sertraline was reduced, the Cmax of the fifth zolpidem dose in the presence of sertraline was significantly increased, and its Tmax was significantly reduced. After five doses of zolpidem, the AUC of sertraline (-6%) and the Cmax of N-desmethylsertraline (+13%) were changed. There were no next-day effects of zolpidem on the Digit Symbol Substitution Test, and both drugs were well tolerated. Overall, coadministration of sertraline 50 mg and zolpidem 10 mg appears to be safe in healthy females but could result in a shortened onset of action and increased effect of zolpidem.