Rats made tolerant to endotoxin are partially protected from the histologic and functional injury that usually accompanies intramuscular administration of glycerol. Glycerol nephrotoxicity appears to correlate with the reductions in renal blood flow and cardiac output which follow injection. Studies were undertaken to determine if endotoxin tolerance would alter these hemodynamic abnormalities. A radiolabelled microsphere technique was employed to measure cardiac output and regional blood flow. Endotoxin-tolerant rats had higher cardiac outputs and renal blood flows and lower renovascular resistances than control rats when studied 90 min after intramuscular glycerol. These observations may partially explain the reduced nephrotoxicity of glycerol in rats made tolerant to endotoxin.