It is generally assumed that febrile nonhemolytic transfusion reactions are an immunologically mediated reaction involving the recipient's plasma and the white cells in the donor unit. This has led to the use of white cell reduction and pretransfusion medication, to try to minimize these reactions. To better understand febrile transfusion reactions, a prospective study was performed in which all patients receiving platelet and red cell transfusions in a tertiary-care medical center were interviewed before and after transfusion to obtain information about the typical presentation of the syndrome. It was found that transfusion reactions were much more frequently associated with platelet transfusion (30.8%) than with red cell transfusion (6.8%, p < 0.0005). The routine use of antipyretics prevented most episodes of fever but did not prevent the occurrence of other symptoms such as chills, cold, and discomfort. The application of logistic regression analysis revealed that the dominant factor determining the risk of a reaction was not white cell contamination, but the age of the component (p < 0.005). The significant relationship between reaction and the increasing age of the component suggests that cytokines released in the component during storage may be responsible for many reactions to blood components.