The effects of hydroxyethyl starch on the final stages of hemostasis were investigated in vivo and in vitro. When compared to control solutions of either 5 percent albumin or isotonic (0.9%) NaCl, 6 percent hydroxyethyl starch (HES) exerted several effects. Results of in vivo studies were as follows: following infusion of 1 liter of 6 percent HES into healthy subjects, fibrinogen and antithrombin-III concentrations fell slightly due to plasma volume expansion and consequent dilution. Concentrations of fibrin monomer and fibrin-fibrinogen degradation products remained unchanged. Thrombin and reptilase clotting times were shortened to indicate rapid detection (and presumably accelerated formation) of fibrin clots. Urokinase-activated clot lysis times were shortened to suggest rapid fibrinolysis. Results of in vitro studies were similar. Shortened thrombin, reptilase, and urokinase-activated clot lysis times were reproduced in vitro by mixing HES, but not albumin or NaCl, with normal plasma. Although these findings qualitatively are similar to those reported previously for dextran, the molecular mechanisms involved and the clinical importance, if any, of the hemostatic effects remain to be defined. Thus, it would be premature to conclude either that HES or dextran exert identical biological effects on hemostasis or that the two agents possess similar clinical properties. HES has an excellent safety record when it has been used during leukocytapheresis and for plasma volume expansion in recommended doses. Its effects when given in larger doses remain to be defined.