Diminished blood selenium levels have been associated with increased risk of gastrointestinal cancers in man, while dietary selenium supplementation reduces the incidence of experimental colon cancer in rats. However, no previously published data are available concerning selenium and the evolution of colon cancer from benign neoplastic colonic polyps through localized and metastatic cancer. To assess any influence of selenium on this polyp to cancer sequence, we measured plasma and erythrocyte selenium levels in colonoscopically and histologically evaluated patients with adenomatous polyps (group I), locally resectable colon cancer (group II), metastatic colon cancer (group III), and selected colonoscopy negative controls (group IV). We found no difference in selenium levels between groups IV versus groups I or II. Likewise, within group I, no difference in selenium was present for different polyp histologies or numbers of polyps. However, selenium levels did drop progressively (p = 0.028, ANOVA) from polyp (group I) to local cancer (group II, p = NS vs group I) to metastatic cancer (group III, p less than 0.05 vs group I or group II). Parallel changes were seen in both plasma and erythrocyte levels, suggesting that these selenium abnormalities are of long duration, reflecting tissue stores, and therefore capable of influencing cancer risk. We conclude that selenium stores may not be an important factor in the de novo formation of benign neoplastic colonic polyps. Although these data suggest that selenium does not affect the polyp-cancer sequence, it is possible that a subset of patients with polyps and the lowest selenium levels are at higher risk for malignant transformation. However, these human data do not support a significant role for selenium in colon carcinogenesis.