The tissue distribution of captopril, an antihypertensive drug possessing a free sulfhydryl group, and its sulfur-conjugated metabolites was studied in rats by gas chromatography-mass spectrometry at 15, 30 and 60 min following a single 10 mg/kg oral dose of captopril. It was found that tissue accumulation of captopril was rapid with both free and oxidized-forms already present at 15 min post-dose. A maximum concentration of captopril was achieved at 30 min in tissues studied, being substantially higher in kidney (14.2 μg/g), with lesser amounts occurring in liver, lung, heart, blood cells, spleen and plasma in that order. Oxidized disulfide forms of captopril were usually present in the same or slightly higher proportion than free captopril except for liver which only contained detectable disulfides at 15 min after oral dosing. S-methylcaptopril was also present at 30 min in all tissues examined with highest levels occurring in liver and kidney (1.05 μg/g) followed by plasma, lung, heart, spleen and blood cells.