This study has demonstrated that hypothermia with or without circulatory arrest produced ultrastructural alterations in the dog brain. Fluid accumulation in the perivascular area and in the neuropil persists for at least seven days. Neurons in all areas of the brain studied are quite resistant to fluid alterations. Minimal changes occurring in neurons appear to be reversible from these studies with no neuronal necrosis, even with cooling to 10°C. Endothelial cells and oligodendrocytes exhibit essentially normal morphology in all experimental groups. Astrocytes and their processes undergo the most severe alterations, with cellular changes greater in dogs subjected to 60 minutes than to 30 minutes of cardiac arrest, and progressive degrees of damage occurring with increases in postpumping time prior to sacrifice. Our studies indicate cytological damage increases for longer periods posthypothermia than earlier reports which noted a resolution at 72 hours of the edema observed at 24 hours. We have demonstrated with the electron microscope (EM) that edema persists for at least seven days.The application of new developments in the pumping technique such as improved filtering of microemboli may reduce the pathological alterations described in this study and aid the clinical management of patients subjected to hypothermia.