We studied the ultrastructural reorganization of hepatocytes and other populations of liver cells after cyclophosphamide treatment. Single administration of cyclophosphamide was followed by significant ultrastructural changes in two major populations of liver cells (hepatocytes and sinusoidal endothelial cells). This treatment was also accompanied by reactive changes in Kupffer cells, lymphocytes, and plasma cells migrating into the spaces of Disse. Cyclophosphamide-induced spatial reorganization of hepatocytes was associated with a progressive decrease in the structural density of mitochondria, significant reduction of the smooth endoplasmic reticulum, and increase in autophagocytosis (e.g., sequestration of glycogen). Intracellular reorganization of endothelial cells was related to the following two factors: damage (necrobiosis) of some cells; and increase in metabolic processes, phagocytosis, and regenerative reactions in other cells.