The disposition of fibronectin in N-2-fluorenylacetamide-induced rat liver lesions was studied by immunohistochemical staining. Male rats were fed the carcinogen for 7 weeks to induce hepatocellular altered foci and then given no chemical or phenobarbital in the diet for 24 weeks until adenomas developed. Regardless of the exposure conditions, the amount of extracellular fibronectin was unchanged in about 60% of the liver altered foci and decreased in about 40%. In contrast, 90% of the adenomas demonstrated a significantly decreased staining pattern for fibronectin. In some adenomas, the fibronectin staining pattern demonstrated irregular, wide, and distorted deposits. In nonlesional regions of the livers of rats exposed to N-2-fluorenylacetamide, the amount of fibronectin was decreased in the centrilobular and midlobular zones. The decrease of fibronectin in hepatocellular altered foci and adenomas demonstrates another abnormality in these lesions, which may be important in their biologic behavior. Foci with decreased fibronectin may have a greater potential to progress to adenomas.