After oral administration, 2 mg/kg in rat and dog, 10 mg in man, of the carbon-14-labeled angiotensin I converting enzyme inhibitor 2-[N-[(S)-1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-(1S,3S, 5S)-2-azabicyclo[3.3.0]octane-3-carboxylic acid (Hoe 498), absorption (rat 56%, dog 43%, man 56%) occurred rapidly and induced maximum blood levels between 0.25 and 1 h. The radioactivity disappeared from the blood in one or two phases with half-lives of 0.6 h in the rat, 1/3.8 h in dog and 0.5/2.9 h in man. Studies in rats have shown that the radioactivity is distributed rapidly to all tissues. Markedly higher concentrations than in the blood were found in the liver, kidneys, and particularly in the lungs. The elimination from the lungs, which showed the highest concentrations until 5 d after administration, occurred with a half-life of 63 h. In rats, 26% of the dose was excreted with the urine and 71% with the feces. About one third of the dose was eliminated with the bile and about 13% was reabsorbed from the bile. The excretion in the breast milk of rats was low. Placental transfer in pregnant rats was low and transient. The radioactivity recovered from the urine of dogs amounted to 15%, that recovered from the feces amounted to 79%. In man, 56% of the radioactivity was excreted with the urine and less than 40% with the feces. Whereas in rat urine one metabolite dominates, the metabolite patterns in urine and serum/plasma of man and dog - which are very much alike - reveal a different biotransformation with three main metabolites. Unchanged Hoe 498, as well as its dicarboxylic acid and other metabolites appear only in low concentrations in this pattern.