Antibodies to autologous alpha-fetoprotein (AFP) were produced in mice by immunization with rat AFP. C57L/J mice with or without such antibodies were inoculated sc or ip with controlled numbers of cells of the syngeneic, AFP-producing, BW 7756 hepatoma. There was a linear relationship between circulating AFP and tumor mass, with elevated AFP being detectable earlier than the tumor. The AFP levels of the immunized mice were generally lower than those of control mice, and tumors could be detected before elevated concentrations of AFP appeared in the circulation. An extensive series of transplantations with varying protocols for immunization did not protect against tumor and did not affect the rate of tumor growth.