A 26-year follow-up of nearly 250,000 US veterans who responded to a questionnaire revealed 4,607 deaths from prostate cancer, providing the largest number of cases to date for evaluating relation to tobacco habits. Cigarette smokers had a significant increase in relative risk (RR = 1.18; 95% confidence interval 1.09-1.28) and a dose response reaching 1.51 among smokers of 40 or more cigarettes per day. Risks were elevated, but not significantly, among users of smokeless tobacco and pipe/cigar smokers. Despite limited data in the literature to support this finding, our study suggests that cigarette smoking may be related to prostate cancer, perhaps through its effect on sex hormone metabolism.