The metabolism of [14C]captopril-L-cysteine was studied in spontaneously hypertensive rats and pure-bred beagles after a single i.v. dose (4 mg/kg). During the first 24 h, concn. of total radioactivity in blood were similar in both species. Captopril was found in small amounts in the blood of both species. In rats, captopril, bound covalently but reversibly to plasma proteins (CP-PR), was the major component in blood (70%), whereas captopril-L-cysteine was a minor component (23%) of the total radioactivity. In dog blood, CP-PR constituted a smaller fraction (45%) of the total radioactivity than in the rat and captopril-L-cysteine was the major component (53%). In 72 h, 89-91% of the dose was excreted in the urine of rats and dogs. Captopril-L-cysteine accounted for 7% (rat) and 68% (dog) of the radioactivity in urine; captopril accounted for 75% (rat) and 7% (dog). Other metabolites were present in the urine of both species. The greater net conversion of captopril-L-cysteine to CP-PR and to captopril in rats helps explain why captopril-L-cysteine is excreted in urine as a major metabolite of captopril in dogs but only a minor one in rats.