We previously showed that providing 30% of nonprotein calories as lipid eliminated glucose intolerance and ameliorated the other troublesome metabolic complications of total parenteral nutrition (TPN): hepatic abnormalities and hypertriglyceridemia. Whether such a mixed-fuel system is as effective as a hypertonic glucose-only TPN fuel system in achieving an anabolic state was tested in 88 consenting patients randomized to either conventional TPN (25% dextrose and 4.25% amino acids) or modified TPN (15% dextrose, fat, and 5% amino acids). Treatment groups were: group A, no surgery, TPN only; group B, postoperative TPN starting 48 hours after surgery; and group C, preoperative TPN, surgery on day 7 and with continued postoperative TPN. In all groups TPN was given for 14 days while patients were given nothing by mouth. Changes in the indexes of body protein metabolism, reflected by nitrogen balance, serum albumin, blood urea nitrogen, and weight, were measured on days 1 and 14. Nitrogen balance improved in patients randomized to either regimen, but there was no significant difference in the degree of improvement. Albumin levels were maintained, and differences between initial and final values were not significant. Blood urea nitrogen increased in all groups (p less than 0.05); however there was no significant difference between regimens. Patients maintained their weight, and fluid balance data indicated no water retention. Observed weight changes were not statistically significant. In each treatment group an anabolic state occurred and gains in measured protein indexes were similar. Isocaloric replacement of 30% of TPN glucose calories with fat was as effective as glucose-only TPN in achieving an anabolic state without the metabolic complications associated with glucose-only TPN.