Although vitamin E can block mutagenesis and cell transformation in vitro and can reduce the number of chemically induced colonic adenomas in mice, previous clinical trials have found no protective effect of vitamin E supplements against colorectal adenomas, and epidemiological studies have found only weak protective effects of dietary or plasma α-tocopherol against colorectal cancer. We previously examined first diagnosis of colorectal adenomas in a sigmoidoscopy screening population and failed to find a protective effect of dietary vitamin E. Because measurements of dietary intake may not be a good proxy of vitamin E status, we assayed plasma α- and γ-tocopherol concentration for 332 subjects with colorectal adenomas and 363 control subjects from this previous sigmoidoscopy-based study. Increasing α- tocopherol and decreasing α-tocopherol levels were associated with decreased occurrence of large (≤1 cm) but not of small (<1 cm) adenomas; however, after adjustment for potential confounding variables, these trends were not statistically significant. A strong trend (P = 0.02) was observed by using the α-tocopherol:γ-tocopherol ratio, which may be a more sensitive indicator of α-tocopherol intake. Subjects in the highest versus lowest quintile of α-tocopherol:γ-tocopherol ratio had an odds ratio of 0.36 (95% confidence interval, 0.14-0.95) for large adenomas. The finding that a high α-tocopherol:γ-tocopherol ratio is associated with decreased occurrence of large, but not of small, colorectal adenomas is consistent with previous findings that α-tocopherol may be protective against colon cancer. A high plasma α-tocopherol:γ-tocopherol ratio may be a better predictor of decreased cancer risk than high plasma α-tocopherol alone.