To investigate whether high serum levels of carotenoids, tocopherols, and folic acid decrease risk of lung cancer in Japanese, we conducted a case-control study nested in the Japan Collaborative Cohort (JACC) Study. A total of 39 140 subjects provided serum samples at baseline between 1988 and 1990. We identified 147 cases (113 males and 34 females) of death from lung cancer during an 8-year follow-up. Of the subjects who survived to the end of this follow-up, 311 controls (237 males and 74 females) were selected, matched to each case of lung cancer death for gender, age and participating institution. We measured serum levels of antioxidants in cases of lung cancer death and controls. Odds ratios (ORs) for lung cancer death were estimated using conditional logistic models. The risk of lung cancer death for the highest quartile of serum alpha-carotene, beta-carotene, lycopene, beta-cryptoxanthin, and canthaxanthin was significantly or marginally significantly lower than for the lowest quartile: the ORs, adjusted for smoking and other covariates, were 0.35 (95% confidence interval (0), 0.14-0.88), 0.21 (0.08-0.58), 0.46 (0.21-1.04), 0.44 (0.17-1.16) and 0.37 (0.15-0.91), respectively. The ORs for the highest serum levels of zeaxanthin/lutein and folic acid tended to be low, but the differences were not statistically significant. Serum total cholesterol was also inversely related to risk of lung cancer death: the OR for the highest vs. the lowest quartile was 0.39 (95% Cl, 0.19-0.79). Higher serum levels of carotenoids such as alpha- and beta-carotenes may play a role in preventing death from lung cancer among Japanese.