The effects of multiple sc injections of cadmium chloride (CdCl2) on the pancreas of two rat strains (Wistar [WF/NCr] and Fischer [F344/NCr]) were studied by histological and immunohistochemical examinations. A high incidence of hepatocytic foci occurred within the pancreata of both strains that was associated with this cadmium exposure. Although pancreatic hepatocytes (PH) were found in both strains, Wistar rats were more susceptible to cadmium-induced PH formation while showing more tolerance to cadmium in general. The highest incidence of PH was 93% in Wistar rats and 50% in Fisher rats. Dose-related increases in incidence of PH occurred at levels of 360-513 mumol Cd/kg. Number of PH foci/rat correlated well with PH incidence. By avidin-biotin immunohistochemistry, PH exhibited rat albumen and a gap junction protein (Connexin32) found in hepatocytes. PH were frequently seen along with pancreatic acinar atrophy (fatty replacement) and interstitial fibrosis. Thus, it appears that cadmium must be considered one of the most efficacious agents for production of PH within the rat pancreas. The ability of cadmium to induce this transdifferentiation is also clearly dose and strain related.