To evaluate the efficacy of nonglucose energy substrates in promoting nitrogen retention and survival in stressed states, two series of studies were done. In study 1, 50 rats underwent cecal ligation/perforation and subsequent infusion for 24 hr with one of four isocaloric (220 kcal/kg/day), isonitrogenous (1.4 g/N/kg/day), isovolemic regimens which differed in caloric source: Glucose (GLU) + long-chain triglycerides (LCT) (50%:50%), GLU + LCT + medium-chain triglycerides (MCT) (50%:32%:18%), GLU + LCT/Carnitine (10 mg/dl) or GLU + LCT + Xylitol (XYL) (33%:33%:33%). The nitrogen-sparing effect of GLU + LCT was not enhanced by the addition of carnitine to facilitate LCT mitochondrial uptake or by MCT to bypass carnitine-dependent transport. In contrast, relative to GLU + LCT GLU + LCT + XYL decreased urinary 3-methylhistidine (3MH) excretion (p less than 0.01), and enhanced nitrogen retention (p less than 0.01 vs GLU + LCT). For study 2, 24 male rats were anesthetized, cannulated for TPN, and given a 25% burn. They were then randomized into three dietary groups. The diets were isocaloric (103 kcal/kg/day) and isonitrogenous (2.0 g N/kg/day) but differed in nonprotein calorie source: GLU + LCT (51%:49%), GLU + Glycerol (51%:49%) and XYL + LCT (51%:49%). As in the septic animals, N balance was best with the xylitol regimen (p less than 0.01). The polyol, xylitol, appears to have a significant nitrogen sparing effect in stressed animals.