Energy production, substrate oxidation, serum protein levels, and weight change were studied in 16 non-steroid treated patients with severe head injury. Patients were evaluated during an average of 31.3 days from hospital admission to discharge. The mean measured energy expenditure (MEE) was 1.40 + 0.5 times predicted energy expenditure. Caloric balance (calories received = calories expended) was achieved by the 2nd week. Despite caloric balance and the administration of at least 1.5 g of protein per kg of body weight per day, the mean nitrogen balance was negative. There was a positive nitrogen balance in only 2 patients. These patients received a mean of 1.43 times the MEE in total kilocalories and 2.3 g of protein per kg of body weight. Fat and protein oxidation exceeded protein and fat administration for 3 weeks postinjury. Albumin levels dropped from a mean of 3.09 + 0.2 on admission to 1.98 + 0.4 within 2 weeks. The initial retinol binding protein levels were within the normal range, and the levels increased over time. There was marked weight loss (mean, 15.6 + 5.9 lb). Head injury induces a profound traumatic response identified by increased energy expenditure, a negative nitrogen balance, weight loss, hypoalbuminemia, and altered substrate oxidation. This response seems to be caused by the head injury alone and is not due to the administration of corticosteroids.