Morbidity and mortality of approximately 90% occurred in a population of pond-reared fingerling striped bass (Morone saxatilis) in northern California. Affected fish had darkened body color, bilateral exophthalmos and abdominal distension. External infections with both Ichthyoboda sp. and Flexibacter columnaris were detected upon necropsy. Internally, the livers were enlarged and pale and a small amount of a serous fluid was present in the abdominal cavity. Microscopic examination revealed panhepatic megalocytosis often with individual hepatocyte degeneration and necrosis. There was also karyornegaly with the presence of irregular, basophilic intranuclear inclusions. Electron microscopic examination of liver sections showed invagination of the nuclear membranes and the presence of multiple, variably sized, membrane bound osmiophilic intranuclear inclusions consistent with lipid accumulation. Similar membrane bound lipid material also occurred within the cytosol and within the cisternae of the endoplasmic reticulum. The endoplasmic reticulum and mitochondria were generally swollen suggestive of sublethal cellular injury. There were no indications of systemic bacterial or viral infections when fish were examined by standard procedures. Mortality among fish moved from the pond to the laboratory declined and then ceased after 8 wk and the progression of the hepatic lesions monitored regularly. Proliferation of small oval cells (putative stem cells) occurred adjacent to foci of degenerative cells prior to regeneration and appearance of morphologically normal hepatocytes. However, multifocal areas of exocrine pancreatic metaplasia also occurred in several surviving fish after 6 mo. Fish surviving for 1 yr had normal hepatic architecture. The etiology of the disease in the pond-reared population was not determined but hepatotoxic agents including pyrrolizidine alkaloids have been associated with similar hepatic lesions in mammals and rainbow trout. Blue green algal hepatotoxins are another possible causative factor since the ponds were eutrophic with abundant algal populations. Experimental studies are now in progress to examine the possible causes and pathogenesis of these hepatic lesions.