The effects of the oxygen-carrier fluorocarbons on myocardial infarct size were assessed in non-exchange-transfused dogs subjected either to a 3-hour occlusion of the left anterior descending coronary artery (LAD) followed by 2 hours of reperfusion (protocol I) or to a 5-hour permanent LAD occlusion (protocol II). Fluorocarbon administration was begun 30 minutes after LAD occlusion and was continued over the entire period of ischemia. After 5 hours, the hearts were excised and areas of necrosis were visualized by triphenyl tetrazolium chloride staining while risk regions were assessed by radiolabeled microspheres injected after coronary occlusion just before the onset of therapy, and further, in protocol I, by thallium-201 perfusion imaging performed at the end of fluorocarbon administration. In protocol I experiments, the ratio of necrotic area to area at risk was 81 ± 35% (mean ± standard deviation) in control saline-treated dogs (n = 6) and 67 ± 27% in fluorocarbon-treated dogs (n = 6) (difference not significant). There was no significant difference between risk regions measured after and before fluorocarbon treatment. In protocol II, the ratio of necrotic area to area at risk was 47 ± 30% in control dogs (n = 5) and 63 ± 29% in fluorocarbon-treated dogs (n = 5) (difference not significant). However, in control dogs, the ratio of necrotic area to area at risk increased from 47 ± 30% in the dogs that underwent permanent occlusion to 81 ± 35% in the group that underwent reperfusion (p < 0.001) while this ratio was similar in the corresponding subsets of fluorocarbon-treated animals. Thus, fluorocarbons did not reduce infarct size compared to untreated controls either in the reperfusion or in the permanent coronary occlusion model, but comparison of data between these 2 models suggests that perfluorochemicals may offer some protection against reperfusion injury. © 1985.