The metabolic fate of oxazepam in the rat is more complex than in larger animal species. Condensation of the diazepinyl ring and phase 1 transformations which lead presumedly via an epoxide to metabolites hydroxylated on the 5-phenyl moiety of oxazepam occurs in addition to glucuronidation, which has often been reported to be predominant in larger species. Unchanged oxazepam is the major compound in plasma, liver, and kidney, but phase 1 and phase ii metabolites also are found. In brain, though, only oxazepam is recognized, and a brain/plasma ratio of approximately 3-5:1 demonstrates that the drug has considerable affinity for that tissue. Excretion of oxazepam and its biotransformation products occurs mainly by the fecal route (70.7 +/- 6.0% of the dose) via biliary secretion. Glucuronides and sulfates of the hydroxylated metabolites and oxazepam and its glucuronide are secreted into bile, but only oxazepam, 4'-hydroxyoxazepam, and unknown polar metabolites constitute most of the fecal radioactivity, suggesting that enterohepatic circulation and intestinal metabolism are significant in the rat.