Spongiosis hepatis (SH), first reported as a distinct lesion associated with certain forms of hepatic neoplasia in rats, has also been induced with chemicals, in a predictable fashion, in small teleost fishes being studied as carcinogenesis research models. The sheepshead minnow (Cyprinodon variegatus), exposed to N-nitro-sodiethylamine (DENA) in sea water, provided the model for the study. The fish developed SH and presented a spectrum of developmental or progressive stages of the lesion over a 140 week holding period following a 6 week exposure to about 57 mg/L DENA. The origin of SH in the fish model is homologous to that in the rat model, both species having the perisinusoidal cell (stellate cells of Ito) in the space of Disse as the cell of origin. Light (LM) and electron microscopy (EM) studies characterized the different pathogenetic stages of SH in liver of the sheephead minnow and revealed a possible late transition of SH to putative polymorphic cell neoplasms. The possible preneoplastic or neoplastic nature of SH from its time of origin in chemically exposed fish to time of appearance of associated presumptive neoplasms is discussed. SH may be a bioindicator of exposure to certain chemicals in some vertebrate species, from fishes to mammals. (Copyright (c) 1991 by the Society of Toxicologic Pathologists.)