The presence of 4 human malignant tumors (1 breast, 1 lung, and 2 colon carcinomas) growing subcutaneously as heterotransplants in nude mice did not significantly affect the body weights of adult animals until the tumors reached very large dimensions (tumor wt greater than 15% of the body wt). However, a colon carcinoma (HT 29) induced a cessation of the natural rate of body weight increase when it grew in young adults (animals weighing approximately equal to 25 g which will gain 6 g or approximately equal to 25% body wt in 1 mo). Calorie restriction at all the levels tested (8, 6, 4, and 2 g/day/mouse) with standard pelletized mouse food produced both weight loss in the animals (with and without tumor) and a lowering of the growth rate of all the 4 tumors tested growing at a subcutaneous site and/or under the kidney capsule. Each tumor responded differently to the calorie restriction. The 4 tumors tested grew equally in both male and female nude mice. Young animals weighing 20 g inoculated with a fifth tumor (MeWo melanoma) exhibited tumor growth inhibition proportional to restriction of calorie intake. Their survival, however, did not improve.