Global ischemia in guinea-pig hearts for 60 to 90 min depressed microsomal and mitochondrial Ca2+ uptake activities. Reperfusion of the 60 min ischemic hearts resulted in incomplete recovery of contractile function and calcium uptake activities of both mitochondrial and microsomal fractions. On the other hand, reperfusion of the 90 min ischemic hearts further depressed the microsomal Ca2+ uptake activity. Coronary occlusion for 90 min in dog hearts was found to decrease microsomal Ca2+-pump and sarcolemmal Na+-K+ ATPase activities. Reperfusion of these regional ischemic hearts further depressed the microsomal Ca2+ uptake and Ca2+-stimulated ATPase as well as sarcolemmal Na+-K+ ATPase activities whereas mitochondrial Ca2+ uptake was increased. Perfusion of rat hearts for 60 min with hypoxic medium resulted in depression of the sarcolemmal Na+-dependent Ca2+ uptake and ATP-dependent Ca2+ uptake activities. Reperfusion of these hypoxic hearts failed to recover the sarcolemmal Na+-Ca2+ exchange and Ca2+-pump activities. These results demonstrate that membrane defects with respect to Ca2+ transport processes in ischemic/hypoxic hearts may be associated with irreversible injury.