Eosinophilia may complicate allogeneic bone marrow transplantation (BMT) after treatment with preparative regimens that include total body irradiation (TBI). This complication is of uncertain significance and has not been reported after treatment protocols which do not contain TBI. We reviewed our experience using busulfan and cyclophosphamide (CY), instead of TBI, as the preparative regimen for allogeneic BMT to study the incidence and relationship to graft-versus-host disease (GVHD) of post-treatment eosinophilia. Fifty-five consecutive patients receiving busulfan 16 mg/kg and CY 120 mg/kg for the treatment of leukemia were reviewed. All patients received non-T cell-depleted, HLA-matched sibling or unrelated donor marrow 2 days after chemotherapy was complete. Cyclosporine (CYA) and methylprednisolone were given to prevent GVHD. Thirty-nine patients surviving 100 days post-transplant were evaluated; 11 (28%) patients developed eosinophilia (defined as an absolute eosinophil count of > 500 x 10(6)) after transplant. Only 2 patients were still taking methylprednisolone at the onset of eosinophilia. At the onset of eosinophilia 5 of these 11 patients (45%) and GVHD that worsened within 2 months. In the other 6 patients (55%), GVHD was not present initially but developed in all 6 patients at a median of 4 months after the onset of eosinophilia. We conclude that eosinophilia can complicate allogeneic BMT not preceded by TBI and that it often heralds the onset of worsening of, or de novo, GVHD.