The availability of hematopoietic growth factors has introduced a new therapeutic modality to the treatment of graft failure after bone marrow transplantation (BMT). However, the clinical value of other therapeutic approaches to graft failure has not been reported in detail. We have studied the outcome of second infusions of BM for treatment of primary and secondary graft failure in 33 patients who received an allogeneic BMT at our institution between 1974 and 1992. Patients had received BM from a related (n = 28) or unrelated (n = 5) donor for hematological malignancy or BM failure. After primary graft failure, 57% (12 of 21) of reinfused patients engrafted and the Kaplan-Meier estimate of survival at 1 year is 24% (CI 6-42%). After secondary graft failure, 33% (4 of 12) of reinfused patients engrafted and survival is 25% (CI 0-50%) at 1 year. Infection, predominantly fungal, was the most frequent cause of death. Acute or chronic graft-versus-host disease (GVHD) developed in 52% of evaluable reinfused patients. We conclude that reinfusion of donor marrow can be an effective intervention in the treatment of primary and secondary graft failure. These data can serve as a comparative historical experience for the assessment of hemopoietic growth factors in the treatment of graft failure.