1 Mast cells and basophils are believed to trigger allergic reactions and anaphylaxis. They rapidly release histamine (H), a typical mediator of in¯ammation, in response to antigens. In the mouse, platelets contain much 5-hydroxytryptamine (5HT), an additional in¯ammatory mediator, while human platelets contain both H and 5HT. Here, we examined the response of platelets in sensitized mice to antigen challenge. 2 Platelets accumulated in the lung and liver almost immediately after intravenous injection of ovalbumin (OVA), in mice sensitized to it, and platelet degranulation occurred during these reactions. 3 These responses of platelets preceded H release from mast cells and/or basophils, occurred at doses of OVA lower than those inducing H release, and contributed to the signs of shock. 4 We reported previously that intravenous injection into mice of LPS (a membrane constituent of gram-negative bacteria) induces a similar platelet response (accumulation of platelets in the lung and liver) and shock. 5 Blood that has passed through the body (other than the digestive tract) passes ®rst to the lungs before being recirculated by the heart, and blood that has passed through the digestive tract passes next to the liver. Thus, our ®ndings suggest that in addition to their role in haemostasis, platelets, tiny anuclear cytoplasts, may be important in both innate and acquired immunity, and that the lung and liver may be the fronts at which platelets wage war on pathogens.