Most previous studies on the inhibiting effect of caloric restriction during promotion of DMBA-induced mammary carcinogenesis have used low to moderate levels of dietary fat, i.e., about 4 to 14% by weight. The current study was designed to test whether a moderate degree of caloric restriction, 25%, would inhibit tumor growth in rats fed the equivalent of 20% dietary fat which approximates human consumption in affluent countries. Rats were fed diets ad libitum that contained 5, 15 or 20% corn oil. Groups of rats were pair-fed to the last 2 groups, but subjected to a 25% caloric restriction. These groups were fed 20 or 26.7% corn oil so that absolute fat intake in the paired groups was identical. Significant inhibition of tumor incidence, tumor weight, tumor burden, body fat deposition, and fasting serum insulin were observed in the 2 calorically restricted groups. We conclude that moderate caloric restriction is significantly more effective in inhibiting tumor growth than is the promoting effect of diets high in fat. Total body weight, body fat and serum insulin concentrations may be better correlates of risk of developing mammary tumors than is dietary fat.