Angiotensin converting enzyme inhibition in heart, kidney, and serum were studied ex vivo after oral administration of lisinopril (10 mg/kg), zofenopril (10 mg/kg), and captopril (30 mg/kg) to rats to study the time course, degree, and sites of inhibition of ACE by a quantitative in vitro autoradiography and enzymatic assay. ACE activity in all regions of the heart, kidney, and serum was markedly reduced 4 h after administration of lisinopril and zofenopril and only partially recovered toward control levels at 24 h. After captopril treatment, ACE activity was partially inhibited in heart, kidney, and serum at 1 h and fully recovered toward control levels in most regions at 24 h. These results suggest that these inhibitors reduce ACE in all regions of the heart and kidney without regional selective inhibition. Lisinopril and zofenopril at these doses produced longer-lasting ACE inhibition than captopril. ACE recovery after ACE inhibitor treatment in serum was faster than in heart or kidney.