The aim of this study was to investigate whether hydroxyethyl starch of medium molecular weight (200 daltons), compared with albumin, has specific effects on blood coagulation and fibrinolysis. A prospective, randomized, double-blind, crossover trial. Laboratory at a university hospital. Ten healthy male volunteers, 23 to 39 yrs old, with no history of hypersensitivity, who had normal physical examinations, and were free of a bleeding disorder. All patients did not ingest any medications for > or = 2 wks before or during the study period. Each volunteer received either 500 mL of hydroxyethyl starch (6% wt/vol, average molecular weight 200 kilodaltons, molar substitution 0.5 [ratio hydroxyethyl groups/glucose units] in 0.9% sodium chloride; average molecular weight of 200 kilodaltons) or a control of 500 mL of human albumin (5% albumin solution). After a washout period of 4 wks, subjects crossed over to the alternate treatment. Blood samples were taken immediately before infusion and 20, 45, 75, 105, 165, 285, 405, and 1485 mins after the infusion started. Hematocrit, the blood coagulation parameters fibrinogen, activated partial thromboplastin time, factor VIII:C, thrombin-antithrombin III complexes, and the fibrinolytic parameters fibrin-split product D-Dimer, tissue type plasminogen activator, urokinase plasminogen activator, plasminogen activator inhibitor, and plasmin-antiplasmin complexes were measured. Except for factor VIII:C levels, which were significantly lower in the hydroxyethyl starch group, no other significant differences in the plasma levels of the parameters mentioned were detected between hydroxyethyl starch and albumin infusions. In one volunteer, who had a low initial factor VIII:C level of 51%, a decrease to 28% at 165 mins during hydroxyethyl starch infusion was found (corresponding albumin value at 165 mins was 41%). a) Medium molecular weight hydroxyethyl starch has a specific lowering effect on factor VIII:C concentrations; this phenomenon may be hazardous to patients who need full hemostatic competence and who receive medium molecular weight hydroxyethyl starch (e.g., as a plasma expander). b) Medium molecular weight hydroxyethyl starch does not specifically influence the activity of the fibrinolytic system.