Captopril is an angiotensin-converting enzyme inhibitor that has been reported to be effective in salvaging post-ischemic reperfused myocardium by its ability to function as a free radical-scavenging agent. A study was performed in the isolated porcine-heart model evaluating the influence of pretreatment with captopril on salvage of myocardium after an induced myocardial infarction. Measurement was carried out of regional and global myocardial function, myocardial high-energy phosphate levels, creatine kinase release, malonaldehyde formation, and 6-keto-prostaglandin F1 alpha generation. In an in vitro preparation, the influence of captopril for scavenging various free radicals was evaluated. A dose-response curve was carried out using this free radical-generating system and differing levels of captopril. Results of the study demonstrate that pretreatment with captopril at a 45-mumol/L level reduced reperfusion injury in the pig heart model. This was manifested by improved cardiac performance, a reduction in creatine kinase release, and reduced malonaldehyde generation. In vitro evaluation of captopril and its free radical-scavenging ability indicated that it is a weak scavenger of superoxide anions (O2-) but behaves as a potent scavenger of hydroxyl radicals (-OH) as well as hypohalite radicals (OCl-). Based on the influence of captopril in reducing lipid peroxidation (decreased malonaldehyde formation) and its documented ability to scavenge -OH as well as OCl-, it is suggested that myocardial preservation in a postinfarction model is due primarily to its free radical-scavenging activity, primarily of the potent free radicals -OH and OCl-.