Protein and energy metabolism were investigated in acutely septic rats. Rats were made septic by cecal puncture and ligation. For the next 24 h they were given one of five parenteral formulations differing only in the nonprotein calorie source. The five calorie sources were 1) glucose, 2) long-chain triglycerides (LCT), 3) a 27:73 mixture of medium- and long-chain triglycerides (M/LCT), 4) a 50:50 mixture of glucose plus LCT, and 5) a 50:50 mixture of glucose plus the M/LCT mixture. The formulations also contained amino acids at a calorie:ratio of 165:1. The results were that N retention was greater with the glucose plus LCT mixture than with glucose alone. With this mixture, N retention increased as calorie intake increased, whereas with glucose, N retention plateaued. In spite of the high glucose load given to the glucose-only groups, there was a significant reduction in endogenous fat in peripheral depots. Lipid loss was least with the glucose plus LCT combination. The M/LCT mixture given alone or with glucose resulted in significantly lower survival rates.