A human colon carcinoma cell line was established from a metastatic lymph node of a patient with hereditary adenomatosis of the colon and rectum (ACR). Cells of this line, designated KMS-4, have been continuously propagated in culture during the past 24 months. The cells growing on the surface of culture dishes showed epithelial features, and, when inoculated into athymic nude mice, produced adenocarcinomas with a morphology similar to that of the original tumor. Electron micrographs showed that the cultured cells have desmosomes and numerous surface microvilli typical of colon epithelium. Chromosomal analysis revealed the cell line to be of human origin with a diploid mode of chromosome number, but the karyotypes examined were all abnormal. Most of the metaphases commonly had such abnormalities as 7p+, 12p+, +13, +16 and 17p+, accompanied by loss of chromosome No. 19 and/or 20, and, interestingly, all the metaphases contained 7p+ and +13. The cells had a log phase doubling time of 48 to 72 h. The cloning efficiency of the cells was 0.06% in the soft agar medium. Neither 12-O-tetradecanoylphorbol-13-acetate nor bile acids enhanced cell proliferation. The cells abundantly secreted CEA protein into the culture medium (700 ng/ml/106 cells during a 48 h period). The present colon carcinoma cell line derived from a genetically defined individual with ACR should prove useful for research in human oncology or genetics.