Introduction: The changes occurring during the initial phase of a circumscribed cryonecrosis of the liver were systematically observed. Material and Methods: Circumscribed necroses were produced in the liver with a copper cryoprobe (Grünenthal, Model H 29, Φ 3,2 mm, operating at −196°C), applied for 30 sec. For light- and electronmicroscopic investiagtions, tissue samples from the frozen area and its surroundings were taken immediately after freezing and at certain time intervals until 24 hours later. Results and Discussion: No important changes were observed immediately after freezing. After 2 to 3 minutes, the frozen tissue had thawed. Considerable stasis occurred within the sinusoids and veins of the affected area. After 2 minutes, the sinusoidal endothelial cells showed a shift towards the lumen and ruptures of their plasma membranes; after 30 minutes, these cells were almost completely fragmented and surrounded by fibrin precipitates. After 30 minutes, hepatocytes showed “optically empty” vacuoles in the cytoplam, swelling of mitochondria (matrix type), disorganization, fragmentation, vesiculation and degranulation of the rough endoplasmic reticulum and pyknosis and karyorrhexis of the nuclei. After 2 hours, the sinusoidal endothelial cells and the hepatocytes bore marks of irreversible lesions and necrosis. At the periphery of the necrotic area there was a narrow zone of hepatocytes with well-preserved nuclear structure, some fatty change, and slight swelling of mitochondria. Simultaneously, a leukocytic infiltrate was present around the damaged tissue, from which leukocytes had penetrated into the necrotic area. After 18 and 24 hours, the peripheral zone with degenerative changes in the hepatocytes showed single cell necroses. The ultrastructural changes described are not specific in themselves; collectively, however — i.e. by the pattern of lesion — they are characteristic and differ from other lethal liver injuries, mainly by the very early necrosis of sinusoidal endothelial cells and the uniformity in degree and extent of the hepatocellular lesions. It is assumed that the most important pathogenetic factor is the formation of relatively large ice crystals within cells and the extracellular area due to recrystallization during thawing. Hypoxemia due to stasis appears to be of minor importance.