Subadult and adult hamsters were inoculated intraperitoneally with 10(6) TCID(50) of yellow fever (YF) virus (Jimenez strain). Four animals from each group were subjected daily to histologic examination for 9 days. The liver showed spotty necrosis on day 3 after infection, which was followed by steatosis and focally confluent necrosis. In surviving hamsters, hepatocyte regeneration began on day 8, which was accompanied by decreasing steatosis. The spleen initially exhibited lymphoid hyperplasia, which was followed by lymphoid depletion and increased phagocytosis by splenic macrophages. Focal pancreatic acinar necrosis and spotty adrenal cortical necrosis were seen transiently between days 5 and 7. Viral antigen was detected immunohistochemically in the liver and the spleen. TUNEL analysis showed a dynamic change of hepatocyte necrapoptosis, with activity corresponding to the severity of disease. The histopathologic changes were more severe in younger (subadult) animals. The YF-hamster model appears to be an accurate and inexpensive experimental system for studying the pathophysiology and treatment of YF.