After oral dosing of 10 mg 8-chloro-6-(2-fluorophenyl)-1-methyl-4H-imidazo[1,5-a][1,4] benzodiazepine (midazolam, Ro 21-3981, Dormicum) labelled with 14C (25 microCi) to 4 human volunteers, the total radioactivity is mainly excreted via the kidneys. Nearly 90% are excreted within 24 h. Main urinary metabolite is the conjugated 1-hydroxymethyl derivative, which amounts to 60-70% of the administered dose within 24 h. Compared to total radioactivity, levels of unchanged drug in plasma are rather low and differ from one subject to the next. Most of the plasma radioactivity consists of the 1-hydroxymethyl compound, most of it in conjugated form. Levels of free metabolite are lower than those of unchanged drug. Radioactivity is rapidly eliminated from plasma. The results of the present oral study seem to indicate significant first-pass metabolism.