Thrombocytopenia as well as hemoconcentration and leukopenia followed by leuko-cytosis were induced after HoGG challenge on HoGG-sensitized mice. Thrombocytopenia was induced within 2min and sustained for 1 day. HoGG-induced thrombocytopenia was not observed until day 10 after sensitization; mice challenged with HoGG dose ≥10μg developed thrombocytopenia. Two types of thrombocytopenia were observed in appropriately sensitized mice. HoGG induced thrombocytopenia at 2min and 60 min, whereas, α-macroglobulin induced thrombocytopenia at 2min, the platelet count of which returned to normal within 60min. Poly (Glu60Ala30 Tyr10) did not induce thrombocytopenia at 2min or 60min. The tracing study by 3H-serotonin labelled platelets demonstrated the 2min-sequestration of platelets in lungs or livers. The HoGG-induced sequestration of platelets at 2min was blocked by high dose heparin or Cobra Venom factor. Platelet activation at 60min was partially inhibited by dexamethasone, rhodostomin synthetic peptide 45–59, or platelet activation factor antagonist (WEB 2086). Furthermore, the thrombocytopenia could be transfered by heat (56°C, 4h)-treated immune sera. This suggests that HoGG-induced, non-IgE-mediated thrombocytopenia in anaphylaxis involves sequestration and activation of platelets. The sequestion in lungs occurs within 2min and can be inhibited by high dose heparin or Cobra Venom factor. The activation of platelets involves platelet activation factor, and fibrinogen receptor.