Groups of estuarine sheepshead minnows (Cyprinodon variegatus) were exposed to 50-60 mg/l N-nitrosodiethylamine (DENA) for five to six weeks. Exposure was stopped and the fish were then transferred to clean, flowing seawater. Induced liver lesions were studied in periodic samples of fish taken during the next 67 weeks of holding. Most of these lesions were compared to their counterpart lesions in the rat. Certain lesions such as hepatocellular carcinomas, cholangiolar carcinomas, spongiosis hepatis (SH), and cholangiofibrosis in the fish have apparent similar cellular origins and morphogenesis to those Lesions in rats, and perhaps in other mammals. SH in the sheepshead minnow apparently arises from perisinusoidal cells and may be a neoplasm of the cell type. The general similarity of response to DENA in sheepshead minnows and rats suggests that the fish has promise as an assay subject for identifying some hepatocarcinogens, and as a sentinel organism for detecting hepatocarcinogens in contaminated coastal waters.