The disposition, distribution and the hepatic first-pass effect of pinazepam and its metabolite N-desmethyldiazepam was investigated in rats. Pinazepam (20 mg/kg) was orally administered by stomach intubation. Plasma and tissue concentrations of the parent compound and metabolite were measured by GLC analysis. Pinazepam was rapidly absorbed (ka = 2.77 hr-1) and converted into N-desmethyldiazepam, plasma levels of which were higher than those of parent compound shortly after administration. The elimination rate constants were 0.20 hr-1 for pinazepam and 0.69 hr-1 for N-desmethyldiazepam. Liver contained the highest concentrations of both compounds. Brain, lung, heart, and kidney preferentially accumulated pinazepam when compared to the gastrocnemius muscle, which accumulated both compounds poorly. The first-pass effect of pinazepam by the liver was studied by analyzing blood from the portal and hepatic veins in rats. Ten minutes after dosing, the mean plasma concentrations of parent compound and metabolite, respectively, were 367.5 and 22.1 ng/ml in the portal vein and 9.8 and 40.7 ng/ml in the hepatic vein. Therefore, rat liver avidly extracted pinazepam from the blood and rapidly metabolized it into N-desmethyldiazepam.