Premazepam, a pyrrolodiazepine with potential anxiolytic properties, behaves as a partial antagonist to diazepam in animal tests. Its pharmacokinetics and metabolism were studied in four healthy volunteers. After oral administration of 30 mg [6-14C] premazepam, the plasma levels of total radioactivity reached maximum concentrations 1-4 h (mean 2 h) following administration. The plasma curve was described by an open one-compartment model, and half-life was 11.5 +/- 1.3 h. Levels of the unchanged compound accounted for about 80% of the total radioactivity up to 24 h. Half-life of the unchanged compound was 7.9 +/- 1.2 h. On the average, 89.6% of the administered radioactivity was recovered in the urine and 2.3% in the feces during the 5 days following administration. Unchanged premazepam accounted for about 70% of the total radioactivity excreted in the urine. Of the three metabolites identified in the urine, none was active in vitro in displacing 3H-diazepam from its forebrain receptors in the rat, indicating that only the parent compound has definite pharmacologic activity.