The activation of platelets and the coagulation mechanism was studied by collecting blood from a standard bleeding time incision at 30-second intervals and measuring the plasma concentrations of fibrinopeptide A (FPA), platelet factor 4 (PF4), and thromboxane B2 (TxB2). FPA was observed in the first samples (30 to 60 seconds) obtained, increased progressively until cessation of bleeding, and was markedly diminished after heparin administration, thus indicating that thrombin formation occurs early in incisional blood. PF4 increased monotonically throughout blood sampling, whereas the major increase in TxB2 appeared near the cessation of bleeding. The initial increase in FPA content occurred normally in patients with deficiencies of either factor IX or VIII, was markedly diminished in patients with factor X or V deficiency, and was delayed in patients with factor VII deficiency. These studies suggest that tissue factor activation of the classic (activation of factor X) extrinsic coagulation mechanism occurs as an early event during the arrest of bleeding from bleeding time incisions. The relation of the aforementioned to platelet activation is less clear because there was no consistent correlation between decreased FPA formation and impaired PF4 secretion or TxB2 production. In fact, the latter were normal in some subjects with the most impaired FPA formation, which suggests that both collagen and thrombin, perhaps synergistically, may contribute to platelet activation during the primary arrest of bleeding.