We tried to detect oncogenes associated with familial adenomatous polyposis by a tumorigenicity assay in nude mice. One polyp and two peripheral blood lymphocyte DNAs out of 12 samples from patients induced Alu-positive tumors. Lymphocyte DNAs from one of 5 healthy people also showed tumorigenic activity. The transforming genes of polyps from a patient and lymphocytes from a normal person were found to be the human N-ras gene. Since these N-ras genes were amplified in nude mouse tumors and did not show any alterations in the nucleotide sequences around codons 12 and 61, it is likely that the tumors were induced by the amplified normal N-ras genes. The transforming sequences from two patients' lymphocytes did not hybridize with 12 known oncogene probes, suggesting that these two genes are novel oncogenes or genes for which we have not yet examined the homology. One oncogene derived from a patient's lymphocytes was partially cloned and shown to be located on human chromosome 7. This gene did not hybridize with the met and erbB1 genes, which are potential oncogenes located on chromosome 7. These data indicate that this gene is a new oncogene.