Sepsis in rats was produced in cecal ligation and puncture. Sixteen hours later, the peritoneal cavity was reopened, the gangrenous cecum removed, and the cavity irrigated with warm saline. Animals which were normotensive then received iv either: (a) saline (controls), (b) glucose (50%) plus saline, or (c) ATP-MgCl2 (12.5 or 100 μmole ATP and 12.5 or 50 μmole MgCl2) with or without hypertonic glucose plus saline. Following the infusion of one of the above, survival was measured over a period of 5 days. The results indicate that there was no statistical difference in the survival rate of rats given saline, glucose, ATP-MgCl2 alone, or lower concentrations of ATP-MgCl2 with glucose. However, infusion of ATP-MgCl2 (100 μmole ATP + 50 μmole MgCl2) plus glucose (ATP-MgCl2-G), resulted in a significant increase in the survival of animals. Thus, the septic hypoglycemic rats required glucose together with higher ATP-MgCl2 concentrations for treatment to be effective. Hepatic and renal ATP levels decreased during sepsis; however, infusion of higher concentrations of ATP-MgCl2 alone or together with glucose resulted in the restoration of cellular ATP levels within 3 hr. Infusion of glucose alone did not restore cellular ATP levels. Reticuloendothelial system (RES) function was depressed during sepsis; however, infusion of ATP-MgCl2-G resulted in the restoration of RES function. The precise mechanism of the salutary effects of ATP-MgCl2-G on survival is not clear. The results presented here indicate that extirpation of the lesion producing the septic process and metabolic support proved helpful without antibiotic treatment. © 1980, All rights reserved.