The purpose of this study was to examine the ultrastructure of the sarcolemma in the normal and severely anoxic rabbit heart with the technique of freeze-fracture. Severe anoxia and subsequent reoxygenation cause a significant decrease (31%) in intramembranous particles (IMP) in the P face of the membrane and a 25% decrease in the E face. P face IMP's are severely aggregated. The decrease in density and the redistribution of IMP's indicate a severely altered Upoprotein structure of the sarcolemma. In addition, the necks of caveolae open and the caveolae become flattened in the plane of the membrane. With reoxygenation, many rupture. Spherical projections of cytoplasmic vesicles appear in the membrane (possibly of sarcoplasmic reticulum or lysosomal origin) and also can be seen to rupture after reoxygenation. When glucose is present in the perfusate, it affords some protec-tion against these structural defects. We propose that the fragmentation or holes in the sarco-lemma reported in severe anoxia are directly related to the structural changes reported in this study.CircRes 47:131-143, 1980