In order to study the effect of blood transfusions on the donor-specific helper T cell repertoire, donor-specific interleukin 2-producing precursors (Th precursors [Thp]) were examined in 10 patients before and after transfusion. These patients were selected to be male, had received no previous transfusions or transplantation, and had no cytotoxic antibodies against MHC antigens in their serum. The limiting dilution curves were linear before as well as after transfusion, showing that only the cell under study was limiting. It was found that the transfusion donor-specific Thp frequencies increased significantly after transplantation in 10 of 10 patients (ratio: 1.5 to 7.1). In addition, the IL-2 production by individual clones tended to be higher after transfusion. In contrast, Thp frequencies against a third-party control showed a small increase in 4 and was unchanged in 6 patients. These data indicate that blood transfusions prime the donor-specific Th compartment.