We evaluated the effectiveness of total parenteral nutrition and placing the "bowel at rest," as compared to that of ad libitum food intake, on nutritional status and tolerance to combined chemotherapy and radiotherapy in a randomized, prospective trial in children with previously untreated malignancy requiring abdominal and pelvic irradiation and chemotherapy. Administration of TPN was found to be safe and efficacious in maintaining the children in good nutritional status during combined therapy; one-third of the control patients became malnourished and required TPN. There was no beneficial effect of "bowel at rest" and TPN on the ability of patients to tolerate combined therapies in terms of decreased toxicity; however, use of TPN was associated with improved adherence to chemotherapy schedules. Following termination of TPN or ad libitum food intake, and while receiving chemotherapy, the majority of the children who had previously received TPN lost significant weight. To date there has been no difference in mortality rate between the control and TPN groups. Although we conclude that TPN per se had little beneficial effect beyond that of maintaining good nutritional status, every child undergoing intensive combined therapy should have early and periodic assessments of nutritional status, so that the early signs of malnutrition can be detected, and the adverse effects of malnutrition can be prevented by nutritional replenishment, by TPN, or by other methods.