Radiation therapy and chemotherapy have little effect on renal-cell carcinomas (RENCAs). We investigated the effect of the tumor vaccination strategy on preventing tumor formation after a challenge with RENCA. The hepatitis surface antigen (HBsAg) was used to enhance the antitumor immunity and tumor vaccination efficiency. RENCA cells expressing HBsAg (RENCA/HBS) were completely susceptible to HBsAg vaccination, which implies that HBsAg vaccination induces specific antitumor immunity against HBsAg- expressing cancer cells. As with HBsAg vaccination, vaccination with irradiated RENCA/HBS retarded tumor formation following a RENCA/HBS challenge. After HBsAg vaccination, the irradiated RENCA/HBS tumor vaccine completely prevented the tumor formation by RENCA/HBS. Tumor vaccination with irradiated RENCA/HBS (5 x 10(4) cells), but not with RENCA, reduced the tumor rate after a challenge with 5 x 10(6) RENCA cells, whereas a lower tumor load was overcome by the RENCA vaccination alone. These results confirm the postulate that RENCA/HBS vaccination elicits an antitumor immune response to some putative antigens or enhances the general immune competence in immunosuppressed renal tumor patients.