The potential of interleukin 2-gene-transfected tumor cells to prevent tumor growth and cure established tumors was evaluated using cells from a spontaneous, invasive, and metastasizing mouse mammary adenocarcinoma. Tumor cells engineered to secrete interleukin 2 initially trigger a local inflammatory reaction that leads to inhibition of established parental adenocarcinomas, as well as an antigenically unrelated fibrosarcoma. The ensuing systemic immunity selectively inhibits subsequent parental cell challenges and cures established parental adenocarcinomas and their lung metastases, although less effectively as the neoplastic mass increases. Multiple injections of interleukin 2-gene-transfected tumor cells may thus be considered a new form of vaccination in the management of minimal residual disease and incipient metastases.