The authors interviewed 428 pathologically confirmed cases of colon cancer and controls matched on age, sex, race, and neighborhood in the New York counties containing the cities of Buffalo, Niagara Falls, and Rochester. Risk of colon cancer in both males and females, studied separately, appeared to increase with the amount of total fats and total calories ingested. In addition, we found the risk to increase with increases in the Quetelet index of relative weight (weight (kg)/height (m)2). Dietary fiber was only equivocally associated with risk. Fats and Quetelet index were associated with increased risk in a regression analysis adjusting each factor for the other, as well as for fiber, age, and socioeconomic status. The same was true for calories and Quetelet index. Future efforts to clarify a possible protective role for fiber and to disentangle the effects of fats and calories need to be undertaken. The fact that calories ingested and obesity are each associated with increased risk suggests the importance of studying calorie expenditure.