Plasma levels of p53 protein were examined by an enzyme linked immunosorbent assay in 184 patients enrolled in a colonoscopy study. The mean levels among 47 individuals with normal colonoscopic examinations and no prior history of colonic neoplasia (0.12 ng/ml) and among 61 individuals with normal colonoscopic examinations and a prior history of colonic neoplasia (0.09 ng/ml) were similar. However, the mean levels among 54 individuals with newly diagnosed colonic adenomas (0.44 ng/ml) and 22 individuals with newly diagnosed colonic carcinomas (0.55 ng/ml) were statistically significantly elevated compared to the normal controls (P < 0.02). Among these tumor patients, the plasma levels tended to increase with increasing adenoma size and with increasing carcinoma stage, although these trends were not statistically significant. Defining a significant positive plasma level as any value greater than ten times background, the percentage of positive samples increased from 4% in the controls to 20% in the adenoma cases to 32% in the carcinoma cases. These results demonstrate that plasma p53 protein levels are elevated in a subgroup of individuals with colonic neoplasia.