High prediagnostic serum beta-cryptoxanthin levels have been found to be associated with reduced risk of lung cancer in a recent cohort study of Chinese men in Shanghai, China. Data on dietary beta-cryptoxanthin, and other specific carotenoids and antioxidants in relation to lung cancer, particularly in non-Western populations, are scarce. The aim of the present study was to assess the roles of dietary antioxidants in the development of lung cancer. Between April 1993 and December 1998, 63,257 Chinese men and women ages 45-74 years in Singapore participated in a prospective study of diet and cancer. At baseline, an in-person interview was conducted using a structured questionnaire for information on usual dietary habits, tobacco smoking, and other lifestyle factors. A Singapore food composition database was used to estimate intake of alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, lutein/zeaxanthin, vitamins A, C, and E, and folate in study subjects. During the first 8 years of follow-up, 482 lung cancer cases occurred among cohort members. High levels of dietary beta-cryptoxanthin were associated with reduced risk of lung cancer; relative to the lowest quintile, the self-reported smoking adjusted relative risks (95% confidence intervals) for the highest quintile were 0.73 (0.54-0.98) among all of the subjects and 0.63 (0.41-0.99) among current smokers. Before adjustment for cigarette smoking, dietary vitamin C was associated with a statistically significant reduction in risk of lung cancer. However the inverse vitamin C-lung cancer association was largely explained by smoking and dietary beta-cryptoxanthin. Other carotenoids (alpha-carotene, beta-carotene, lycopene, and lutein/zeaxanthin), vitamins A and E, and folate were not associated significantly with lung cancer risk after adjustment for cigarette smoking. We recognized that potential measurement errors in cigarette smoking may exert an effect on the dietary beta-cryptoxanthin-lung cancer association. After additional adjustments were made for the residual confounding by smoking using statistical models, about 15-40% reduction in risk of lung cancer was seen for subjects in the highest versus lowest 10th percentile of dietary beta-cryptoxanthin. The present study lends additional credence to prior experimental and epidemiological data in support of the hypothesis that dietary beta-cryptoxanthin is a chemopreventive agent for lung cancer in humans.