Antioxidant micronutrients may have chemopreventive effects. The authors examined the associations between prediagnostic blood levels of micronutrients and prostate cancer risk in two nested case-control studies of 9,804 and 10,456 male residents of Washington County, Maryland, who donated blood in 1974 (CLUE I) and 1989 (CLUE II), respectively. Until 1996, 182 men for whom adequate serum remained for assays in the CLUE I cohort and 142 men in the CLUE II cohort developed prostate cancer. Each case was matched with two controls by age, gender, race, and date of blood donation. In both cohorts, cases and controls had similar concentrations of alpha-carotene, beta-carotene, total carotene, beta-cryptoxanthin, lutein, lycopene, retinol, and ascorbic acid; serum alpha-tocopherol was weakly associated with prostate cancer risk. Higher retinyl palmitate concentrations were associated with a lower risk in CLUE I but not CLUE II. In CLUE I, cases had lower concentrations of gamma-tocopherol than did controls (p = 0.02), but no dose-response trend was observed. A strong inverse association between gamma-tocopherol and prostate cancer risk was observed in CLUE II. Findings do not replicate previous reports of a protective association between lycopene and prostate cancer, but they suggest potential chemopreventive effects of gamma-tocopherol on prostate cancer.