Changes in the hepatocytes of male hamsters (Mesocricetus auratus) and jirds (Meriones unguiculatus) at 220 days after experimental infection with the liver fluke Opisthorchis viverrini were studied by light and electron microscopy. The hepatocytes of the control group were characterized by an intracellular compartmentation. A globular nucleus was located centrally. The main features of the perinuclear zone were the cisternae of the rough endoplasmic reticulum (RER) and interjacent mitochondria, lysosomes, and peroxisomes. The peripheral cell region was dominated by glycogen fields and scattered lipid droplets, which were surrounded by anastomosing tubules of the smooth endoplasmic reticulum (SER). An immense proliferation of the SER was striking in the hepatocytes of animals infected with O. viverrini. Coincidentally, the intracellular compartmentation disappeared. Glycogen rosettes, RER, lysosomes, and lipid droplets were distributed irregularly all over the cell, the latter being observed more frequently than in control animals. The nuclei showed lobe-like protrusions and were enlarged. The mitochondria were often dumbbell-shaped and showed pathologic degenerations up to lysis. Our results resemble those of numerous investigations concerning hepatocellular alterations caused by N-nitroso compounds. Therefore, these observations suggest a synergistic effect for trematode infection and N-nitroso compounds in the pathogenesis of opisthorchiasis. The cellular alterations observed in the hepatocytes of Opisthorchis-infected animals together with the accumulation of intermediate filaments seen in the adjacent bile-duct epithelia and in the epithelium of the gall-bladder seem to indicate a disturbance of the cell metabolism and might be related to a neoplastic transformation.