The primary limitations of granulocyte transfusions include low component cell dose and leukocyte incompatibility. Component cell dose improved with granulocyte colony-stimulating factor (G-CSF) mobilization, and the transfusion of G-CSF-mobilized, human leukocyte antigen (HLA)-matched granulocyte components resulted in significant, sustained absolute neutrophil count (ANC) increments. However, the effect of leukocyte compatibility on outcomes with G-CSF-mobilized granulocyte transfusions is unclear. The objectives were to determine the effect of leukocyte compatibility on ANC increments and selected clinical outcomes after transfusion of prophylactic, G-CSF-mobilized granulocyte components into neutropenic recipients of autologous peripheral blood stem cell (PBSC) transplants. Beginning on transplant day 2, 23 evaluable recipients were scheduled to receive 4 alternate-day transfusions of granulocyte components apheresed from a single donor given G-CSF. G-CSF was also given to recipients after transplantation. Recipient ANC was determined before and sequentially after each granulocyte transfusion to determine the peak ANC increment. Leukocyte compatibility was determined at study entry only by a lymphocytotoxicity screening assay (s-LCA) against a panel of HLA-defined cells. Eight recipients had positive s-LCA. On days 2 and 4, the mean peak ANC increments after granulocyte transfusion were comparable between the cohorts with positive and negative s-LCA. However, the mean peak ANC increments on day 6 (246/microL vs 724/microL; P =.05) and day 8 (283/microL vs 1079/microL; P =.06) were lower in the cohort with positive s-LCA, in spite of the transfusion of comparable component cell doses. Adverse reactions occurred with only 5 of 87 (5.7%) granulocyte transfusions and were not associated with leukocyte compatibility test results. Platelet increments, determined 1 hour after granulocyte transfusion, were comparable between the cohorts. Although the 2 cohorts received PBSC components with similar CD34(+) cell doses, the cohort with a positive s-LCA had delayed neutrophil engraftment and a greater number of febrile days and required more days of intravenous antibiotics and platelet transfusions. Leukocyte incompatibility adversely affected ANC increments after the transfusion of G-CSF-mobilized granulocyte components and clinical outcomes after PBSC transplantation.