Six healthy fasted volunteers each received oral doses of a placebo, 1 mg and 2 mg loprazolam with one week between treatments using a double-blind balanced crossover design. Serum samples were obtained at selected times after dosing for measurement of loprazolam using a combined high-performance liquid and gas chromatographic assay. Drug effect was also measured at the corresponding times using self-assessment scales and psychomotor tests. The serum levels of loprazolam followed a somewhat irregular shape with secondary and tertiary peaks possibly associated with food intake. The maximum serum levels of loprazolam following 1 mg and 2 mg doses of the drug (6.0 +/- 2.6 and 11.3 +/- 2.9 ng/ml, respectively) occurred at approximately one hour after dosing. Both the maximum serum levels and the area under the curve of loprazolam measured to six hours increased in direct proportion to dose. Statistically significant drug effects were seen after 2 mg loprazolam, although the subjects also appeared sedated after 1 mg doses. There appeared to be a good correlation between the logarithm of the serum concentration of loprazolam and effect which suggested that the hypnotic activity of the drug was not mediated via a long-lived metabolite. A threshold serum concentration associated with evident sedation was observed at approximately 3 ng/ml.