The influence of food on the absorption of midazolam, a new benzodiazepine derivative, was investigated in 18 healthy volunteers in a four-way, randomized, crossover study with a one-week washout period between treatments. Single 15-mg oral doses of midazolam were administered one hour before, with, and one hour after a standard meal as well as under fasting conditions (control). Following serial blood sampling over the next 24-hour period, midazolam plasma concentrations were determined by gas chromatography and mass spectrometry for pharmacokinetic evaluation. The maximum plasma concentration (Cmax), time of maximum concentration (tmax), lag time prior to absorption (tlag), area under the plasma concentration-time curve (AUC), and elimination rate constant of midazolam and 1-hydroxymethylmidazolam were determined. Significant changes in these parameters were not found when midazolam was taken one hour before or with a meal as compared with the control condition. Significant changes in the Cmax, tmax, and AUC parameters for both midazolam and its metabolite were seen when midazolam was ingested one hour after a meal: There was a delayed and reduced rate of absorption as well as a small reduction in the extent of absorption. Thus, ingestion of midazolam within one hour after a meal may result in a delay in the onset of the pharmacologic effect. These changes may be of some clinical significance in that they may potentially delay the onset of sleep.