We conducted a series of case-control studies to investigate the risks of 16 cancer types in relation to occupational physical activity. These studies were based on Missouri Cancer Registry data for 17,147 White male cancer patients registered between 1984 and 1989. Colon cancer risk was increased for both the moderate (odds ratio (OR) = 1.1; 95% confidence interval (CI) = 1.0, 1.3) and low (OR = 1.2; 95% CI = 1.0, 1.5) activity levels. Similar elevations were observed for prostate cancer at the moderate (OR = 1.1; 95% CI = 1.0, 1.3) and low (OR = 1.5; 95% CI = 1.2, 1.8) levels of activity, and for cancer of the testis at the low activity level (OR = 2.2; 95% CI = 1.3, 3.7). An opposite trend (p less than 0.01) was noted for lung cancer, which showed decreased risk at the moderate (OR = 0.9; 95% CI = 0.8, 1.0) and low (OR = 0.8; 95% CI = 0.6, 0.9) activity levels. These associations suggest that further study of the relationship between physical activity and site-specific cancer risk is warranted.