Genetically modified, IL-2-producing tumor cells have been shown to regress in vivo and immunize mice against subsequent challenge with parental tumor. We investigated whether IL-2-producing tumor cells may serve as immunotherapy of established tumors in mice. MCA 205 and MCA 203, weakly immunogenic murine sarcomas of B6 origin, were transfected with the pBMGNeo-mIL-2 vector containing the murine IL-2 cDNA. Mice receiving intraperitoneal injections of the parental sarcoma cells developed ascites and died within 4 weeks. The intraperitoneal injection of IL-2-producing tumor cells significantly prolonged survival and, moreover, significantly reduced the number of established pulmonary metastases. The specificity of this effect was indicated by the unaltered course of disease in mice that were injected with unrelated IL-2-producing tumor cells. FACS analysis of peritoneal cells obtained from treated mice showed a predominance of Vbeta3-positive cells. In a 4 h 51Cr release assay, these Vbeta3-positive cells exhibited tumor-specific cytotoxicity and also nonspecific effector cells are shown to be involved in tumor rejection.