Primary non-engraftment or early rejection after transplantation of haematopoietic stem cells represent life-threatening complications of allogeneic stem cell transplantation. Management of early graft failure has been problematic, as the risk of fatal infectious complications increases with the time of pancytopenia and as a second transplant preceded by a conventional myeloablative conditioning regimen has been associated with high rates of cumulative organ toxicity. For paediatric patients with early graft failure following the transplantation of highly purified major histocompatibility complex (MHC)-disparate haematopoietic stem cells, we have evaluated an immunosuppressive OKT-3/methylprednisolone-based reconditioning regimen with low toxicity in preparation for a secondary transplant of purified haematopoietic stem cells from the same donor. This report presents the results from a 4-year pilot study including six patients with early graft failure. The results demonstrate that this antibody-based regimen can be used effectively to prepare patients for secondary transplantation. Successful engraftment after a second transplant procedure was achieved in five of these six high-risk patients. The median interval between first and second transplant was 27 d (range 22-51 d), and the median time for engraftment was 10 d (range 9-13 d). Chimaerism analysis of microsatellite regions by polymerase chain reaction (PCR) demonstrated complete donor chimaerism in four of these patients within the first month after secondary transplant and revealed mixed chimaerism in one patient who converted to complete chimaerism after T-cell add-back.