Previous studies of nutritional support in cancer patients have applied parenteral techniques for relatively short periods. The purpose of this prospective, randomized trial was to evaluate the efficacy of long-term enteral alimentation in patients at high risk for malnutrition during oncologic treatment. Forty patients with inoperable squamous carcinoma of the nasopharynx and oropharynx were randomized to either optimal oral nutrition or to intensive nasogastric tube feedings during radiation therapy for an average of 8 weeks. Dietetic counselling and oral supplements were provided to both groups. Body weight, dietary intake, and toxicity to therapy were assessed weekly; and serum protein concentrations and anthropometric measurements were made at the time of entry, during the fourth week, at the conclusion of radiation therapy, and 1 month after radiation therapy. Tumor status was assessed at the conclusion of radiation therapy and during routine follow-up, which ranged from 9 to 39 months. The 35 evaluable patients (18 tube fed and 17 orally fed) were comparable with regard to age, disease site, and total radiation dosage, but the tube group had more stage IV patients and a greater median radiation field size. The tube fed group showed no difference in the partial tumor response rate compared with the complete tumor response rate (16 of 18 patients versus 14 of 17 patients), a slightly longer duration of response in those who had recurrence compared with those without recurrence (4.5 months versus 3.4 months) and a similar overall survival pattern to that of the orally fed group. Compared with the orally fed group, the tube fed group had a higher mean caloric intake (39 kcal/kg per day versus 30 kcal/kg per day, p less than 0.001), mean protein intake (1.4 versus 1.1 g/kg per day, p less than 0.01), and in the oropharynx cancer patients, less mean body weight loss (0.6 percent versus 6.1 percent, p less than 0.04) during treatment. The tube fed patients maintained mean mid-arm circumference and recovered mean serum albumin levels after radiation therapy in contrast with the orally fed group. Intensive outpatient tube-feeding nutritional support during radiation therapy in patients with advanced inoperable squamous cancer of the oropharynx significantly improved mean weight maintenance, mean caloric and protein intake, and mean serum albumin levels compared with patients who received optimal oral nutrition. Tumor response to radiation therapy, however, was unchanged.