Because energy-contributing nutrients are highly correlated with total energy, the association with colon cancer from energy versus other components of energy-providing nutrients is often not clear. Dietary data from a population-based case-control study of colon cancer were analyzed in subjects from California, Utah, and Minnesota in 1991-1994 to assess the colon cancer risk associated with consumption of energy, fat, protein, and carbohydrate. After adjustment for long-term physical activity, total energy intake increased risk of colon cancer in men (odds ratio = 1.74, 95% confidence interval 1.14-2.67 for highest vs. lowest quartile) and in women (odds ratio = 1.70, 95% confidence interval 1.07-2.70). Various methods of analysis suggested that intakes of individual sources of energy (dietary fat, protein, and carbohydrate) were not associated with colon cancer risk after total energy intake was taken into account. People who consumed a high-calorie diet that was dense in fiber and calcium appeared to be at lower risk than people with the same caloric intake who consumed smaller amounts of dietary fiber and calcium. Individuals with a first-degree relative with colorectal cancer, especially those diagnosed at a younger age, were at a greater risk from a diet high in energy than were individuals without a family history of colorectal cancer.