Febrile responses are a common and sometimes life-threatening occurrence in patients receiving platelet transfusions. The cause is largely unknown. We showed that CD154 is present at 3000-7000 ng/L in the supernatant of nine preparations of human platelets used for transfusions and induces prostaglandin E-2 synthesis in human fibroblasts. Since CD154 is a potent Inducer of the cyclo-oxygenase-2 enzyme and prostaglandin E-2, the main fever inducers, infusion of platelet preparations containing CD154 may incite febrile responses.