Hydroxyethylstarch (HES) is being used increasingly in clinical hemorrhagic shock. Since patients in shock are at high risk of subsequent infection, concern has been voiced about possible adverse effects of HES on the reticuloendothelial system (RES) and host defenses against sepsis. We examined this issue in male albino Holtzman rats given HES or saline (60 ml/kg) i.v. RES function was evaluated 24 and 48 h after HES administration by measuring the intravascular clearance rates (t/2) and organ retention of 131I-triolein lipid emulsion. Neither the intravascular clearance rates nor organ retention of the lipid emulsion was affected at 24 or 48 h after HES. In another group or rats, sepsis was produced by cecal ligation and puncture 2 d after HES or saline infusion. The survival rates were 41% and 43%, respectively, in the saline- and HES-treated animals. These studies reveal no deleterious effects of clinically relevant volume of HES on either RES function or host resistance to sepsis.