In a study of the association between circulating .alpha.-fetoprotein concentrations and spontaneous hepatocellular carcinomas. C3H-Avy fB mice, which with age consistently demonstrate a rapidly increasing incidence of hepatic cancer were examined. Although elevated .alpha.-fetoprotein levels are observed in association with the majority of these tumors, no elevation of .alpha.-fetoprotein was observed during the life course of nontumor-bearing mice despite their age dependent risk for hepatic cancer. Whatever the evolutionary or age related biological changes may be that lead to tumor formation in this mouse, they are not linked to the synthesis of significant amounts of this oncofetal protein.