The effects of injury with hemorrhagic shock on the clotting and fibrinolytic systems were studied serially in 22 patients receiving 21 ± 13 transfusions and 1.26 ± 0.58 L of fresh frozen plasma (FFP) during operation (OR). The PT, aPTT, thrombin time (TT), fibrinogen (FI), factors V (FV) and VIII (FVIII), fibrin(ogen) split products (FSP) and fibrin monomers were measured in OR and after OR at 6 and 15 hours, days 2 and 4, and at convalescence (25 days). The TT, PT, and aPTT were were prolonged in OR and reflected the low FI, FV, and FVIII, respectively. After OR, clotting times and factor levels returned toward normal. By day 4 and convalescence, FI, FV, and FVIII exceeded normal levels.FSP levels were normal in OR. After OR FSP rose progressively through day 4 when all patients had levels > 10 mcg/ml and most patients had levels above 40 mcg/ml. Fibrin monomers were absent until the 15-hour study after which a small number of patients had monomers through the convalescent study. The acute fall in clotting factors is likely due to increased hemostatic demands, plasma dilution from resuscitation, and extravascular relocation from shock-induced extravascular expansion. Later factor restoration likely reflects enhanced hepatic synthesis, factor half-life, capillary selectivity retaining large molecular weight factors, and intravascular relocation from abundant extravascular stores. Throughout this biphasic response, the clotting times reflect factor levels. Fibrinolysis contributes little to these changes.