Liver cytotoxic alterations of adult medaka (Oryzias latipes) following short-term bath exposure (48 hr) to 500 mg/L diethylnitrosamine (DEN) were studied (days 3-21) by electron microscopy and cytochemistry. Control medaka displayed hepatic sexual dimorphism as described for other sexually active fish. Following DEN exposure, decreased glycogen stores with loss of cellular compartmentation obscured sexual dimorphism. A spectrum of organelle alterations, previously not reported in livers of fish, was seen. Early changes in hepatocytes included: nuclear lipid inclusions, nucleolar changes, decreased amounts of granular endoplasmic reticulum (GER), increased fractionation and steatosis of GER, proliferation of smooth ER and lysosomes, reduction in number and content of particulate lipoproteins and vitellogenin in Golgi vesicles, and reduction in number and staining intensity of peroxisomes. At day 14 and/or 21, partial to complete reversal of the above alterations indicated hepatic recovery, and fewer necrotic cells were seen at day 21 versus day 14. Lesions that did not resolve during this study were altered mitochondria and areas of spongiosis hepatis that developed at day 8 and continued to increase throughout the study. Infiltration of lymphocytes, granulocytes, and large numbers of macrophages were late changes. The description, timing, and duration of lesions are of value for consideration as biomarkers of exposure and effect in aquatic toxicology.