To examine the association between serum nutrients and the development of bladder cancer we measured selenium, alpha-tocopherol, lycopene, beta-carotene, retinol, and retinol-binding protein in serum collected from 25,802 persons in Washington County, MD, in 1974. Serum samples were kept frozen at -70 degrees C. In the subsequent 12-year period, 35 cases of bladder cancer developed among participants. Comparisons of serum levels in 1974 among cases and two matched controls for each case showed that selenium was significantly lower among cases than controls (P = 0.03), lycopene was lower among cases at a borderline level of significance (P = 0.07), and alpha-tocopherol was nonsignificantly lower (P = 0.13). For selenium there was a nearly linear increase in risk with decreasing serum levels (P = 0.03). When examined by tertiles, the odds ratio associated with the lowest tertile of selenium compared to the highest tertile was 2.06. Serum levels of retinol, retinol-binding protein, and beta-carotene were similar among cases and controls. These results support a role for selenium in the prevention of bladder cancer.