It is well known that reticuloendothelial system (RES) function is depressed following thermal injury. Since previous studies have shown that adenosine triphosphate (ATP)-MgCl2 restored the depressed RES function following hepatic ischemia, the present study was undertaken to determine whether administration of ATP-MgCl2 following thermal injury would have any beneficial effects on the RES function. Thermal injury in rats was produced by immersing 30% of the skin surface area in 95°C H2O for 12 sec. Immediately following this, the rats received saline s.c. and 0.25 ml of ATP-MgCl2 (12.5 μmol each) or an equivalent volume of saline i.p. RES function was evaluated by measuring the intravascular clearance of 131I-triolein-labeled gelatinized test lipid emulsion. The intravascular half-time (t/2) in the burned saline-treated rats was double that of control rats at 1 and 3 days post-burn, suggesting that significant depression in RES function occurred following thermal injury. At 5 days post-burn, although the t/2 was lower than at 3 days post-burn, it was still significantly higher than controls. Administration of ATP-MgCl2 following burn injury resulted in a t/2 and phagocytic index values similar to controls, indicating that impairment of phagocytic activity of the RES function following thermal injury was reversed with treatment.