Two lines of evidence have suggested that the loss of tumor suppressor gene function contributes to the multi-step process of tumorigenesis. Tumorigenicity and transformed phenotypes are frequently suppressed in somatic cell hybrids of tumor and normal cells. Consistent chromosomal aberrations indicating gene losses and mutations have been found in hereditary and sporadic human tumors. Tumor suppressor genes can be molecularly cloned, even if the encoded protein products have not been characterized biochemically. Here we describe a functional assay based on DNA transfection permitting the molecular identification of candidate human tumor suppressor genes (R. SCHAFER et al., Proc. Natl. Acad. Sci. USA 85, 1590-1594, 1988). A molecular clone has been identified capable of suppressing the neoplastic phenotype induced by an oncogene belonging to the family of ras genes, whose activation is frequently found in tumors.