Background: Skills performance impairment after acute doses of zolpidem (a short-acting, nonbenzodiazepine hypnotic), alone and with alcohol, was evaluated in 24 subjects. The study was designed to test whether the effects of zolpidem and alcohol are simply additive or reflect potentiation. Method: Healthy male volunteers participated in a randomized, six-way crossover study of placebo, zolpidem 10 mg, or zolpidem 15 mg in combination with a placebo beverage or an alcohol dose selected to attain a peak blood alcohol concentration of 0.08% (drug administered double-blind; beverages administered single-blind). A laboratory test battery of four tasks measured concurrent information processing ability (divided attention task), information processing rate (visual-backward masking task), immediate memory (Sternberg task), and sustained attention (vigilance task). The battery was repeated three times to measure peak (+45 minutes), postpeak (+130 minutes), and residual (+230 minutes) treatment effects after each dosing. Results: Performance on each test-battery task was significantly impaired (p <.05) by both alcohol and zolpidem (combined and each given alone) during the peak-effect assessment. Residual effects were not observed, with the exception of significant alcohol and drug effects on divided attention performance (p <.05). Analysis of variance tests revealed significant main effects of alcohol and zolpidem, but no significant alcohol-by-drug interactions were found for any measure of skills performance. In general, additive effects of alcohol were detected with zolpidem 10 mg but not with zolpidem 15 mg. Conclusion: Although some additive effects of alcohol on performance skills were seen with the lower 10-mg dose of zolpidem, no nonadditive effects were found. That is, alcohol does not appear to potentiate the effects of zolpidem on the various performance skills tested in this population and at the doses and times evaluated. With the exception of persisting deficits (at 4 hours postdose) on the more demanding divided attention task, all other findings were consistent with evidence that zolpidem is a short-acting hypnotic drug.