The metabolism of [14C]captopril has been investigated in vitro and in vivo in male Wistar rats. The formation of conjugates of [14C]captopril with plasma proteins was observed both in vitro and in vivo: 180 min after intravenous infusion of [14C]captopril 35 +/- 5% of total radioactivity was covalently bound to plasma proteins. The fate of [14C]captopril-plasma protein conjugates was investigated in vivo. [14C]Captopril was incubated in vitro with rat and human plasma and the resulting captopril-protein conjugates were infused into male rats. The plasma concentration of [14C]captopril-rat plasma protein conjugates declined monoexponentially with a half-life of 71.1 +/- 2.2 min. After 180 min 28 +/- 3% of the radioactivity was excreted in urine, largely as [14C]captopril-cysteine mixed disulphide (67%). Thus although captopril readily forms covalent bonds with plasma proteins the resulting conjugates dissociate in vivo. The toxicological implications of these findings are discussed.