Evaluation of foci of cellular alteration is utilized in short-term and mid-term rat liver models to assess chemicals for potential carcinogenic effects. Such foci are morphologically defined and readily identified by a variety of histological stains. No single morphological marker appears capable of identifying all foci because of their phenotypic heterogeneity. Since most rodent hepatocarcinogens induce an increase in the size and/or the number of foci prior to tumor appearance, foci are believed to be precursors to hepatic tumors. The size, number, phenotype and conversion rate of foci to tumors is chemical dependent. Despite certain limitations, the quantitation of rat liver foci provides a useful means to study the mechanism of action of selected chemicals and assess their carcinogenic potential.