Peripheral blood lymphocyte cultures from 23 individuals with polyps and 10 age-matched controls were cytogenetically studied. Of 23 individuals with polyps, 13 were males and 10 females. The age distribution of these patients was between 22 and 84 yr, with a medium age of 49.6 yr. Chromosome 5 was involved in structural rearrangements in 10 of the 18 patients with adenomatous polyps (55.5%). All those who showed involvement of chromosome 5 alterations had either adenomatous polyps or Gardner's syndrome, and two had colon adenocarcinoma. Of the remainder who did not show involvement of chromosome 5, eight had adenomatous polyps and five had hyerplastic polyps (non-neoplastic). Of the 10 control samples, only one showed alteration of chromosome 5. Of the 10 adenomatous polyp subjects that showed chromosome 5 defects, two had translocations of chromosome 5 and the short arm of 17. Chromosome 5 was broken 13 times (5 times in the q arm and 8 times in the p arm). Based on our present cytogenetic data, we tentatively conclude that lymphocyte metaphases may be used to identify colon cancer-predisposed individuals.