A population-based case-control study was conducted in Utah to test the hypothesis that calcium decreases the risk of developing colon cancer. A total of 231 cases and 391 controls were identified and interviewed between 1979 and 1982. A quantitative food frequency instrument was used to ascertain individual dietary intake two years prior to diagnosis for the cases and two years prior to interview for the controls. Calcium, calcium per 1,000 calories, and total dairy product consumption were used as indicators of dietary calcium intake. Categories of dietary intake were determined by the distribution of these variables in the control population. A protective effect was observed for males for intake of calcium (odds ratio (OR) = 0.48), calcium per 1,000 calories (OR = 0.35), and total diary products (OR = 0.49). The magnitude of the protective effect from calcium intake increased after adjusting for intake of calories (OR = 0.41), protein (OR = 0.31), and fat (OR = 0.46). Calcium provided less of a protective effect in females, with the odds ratio for calcium being 0.50, 0.55, and 0.56 after adjusting for calories, protein, and fat, respectively. Risk associated with calories, protein, and fat also increased after adjusting for calcium. Of interest is an odds ratio of 5.30 in males for protein after adjusting for calcium. A biologic mechanism is presented to help explain the role of calcium in the development of colon cancer.