Background: Experimental and epidemiologic investigations suggest that a-tocopherol (the most prevalent chemical form of vitamin E found in vegetable oils, seeds, grains, nuts, and other foods) and (3-carotene (a plant pigment and major precursor of vitamin A found in many yellow, orange, and dark-green, leafy vegetables and some fruit) might reduce the risk of cancer, particularly lung cancer. The initial Findings of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC Study) indicated, however, that lung cancer incidence was increased among participants who received p-carotene as a supplement. Similar results were recently reported by the Beta-Carotene and Retinol Efficacy Trial (CARET), which tested a combination of (3-carotene and vitamin A. Purpose: We examined the effects of a-tocopherol and p-carotene supplementation on the incidence of lung cancer across subgroups of participants in the ATBC Study defined by base-line characteristics (e.g., age, number of cigarettes smoked, dietary or serum vitamin status, and alcohol consumption), by study compliance, and in relation to clinical factors, such as disease stage and histologic type. Our primary purpose was to determine whether the pattern of intervention effects across subgroups could facilitate further interpretation of the main ATBC Study results and shed light on potential mechanisms of action and relevance to other populations. Methods: A total of 29 133 men aged 50-69 years who smoked five or more cigarettes daily were randomly assigned to receive a-tocopherol (50 mg), P-carotene (20 mg), atocopherol and P-carotene, or a placebo daily for 5-8 years (median, 6.1 years). Data regarding smoking and other risk factors for lung cancer and dietary factors were obtained at study entry, along with measurements of serum levels of atocopherol and P-carotene. Incident cases of lung cancer (n = 894) were identified through the Finnish Cancer Registry and death certificates. Each lung cancer diagnosis was independently confirmed, and histology or cytology was available for 94% of the cases. Intervention effects were evaluated by use of survival analysis and proportional hazards models. All P values were derived from two-sided or p-carotene supplements prevents the occurrence of lung cancer (7). a-Tocopherol is the most prevalent chemical form of vitamin E that occurs naturally in vegetable oils, seeds, grains, nuts, and other foods, and P-carotene is a plant pigment and major precursor of vitamin A found in many yellow, orange, and dark-green, leafy vegetables and some yellow fruit. The initial cancer-and mortality-related findings of the ATBC Study have been reported (2,3) and indicated no reduction in the incidence of or mortality from lung cancer among participants who received either a-tocopherol or P-carotene as a supplement. Instead, an increase in incidence was observed among participants who received p-carotene (20 mg daily). A similar result for P-carotene was recently reported by the Beta-Carotene and Retinol Efficacy Trial (CARET), which ha...