Seventy percent of children with acute lymphoblastic leukaemia (ALL) who may benefit from bone marrow transplant (BMT) lack a human leucocyte antigen (HLA)-matched related donor (MRD). For these children, BMT from a matched unrelated donor (MUD) represents a therapeutic option. We reviewed the course of 62 children with ALL who received fully matched marrow allografts at our institution between 1990 and 1998: 36 with MRDs and 26 with MUDs. Clinical characteristics were similar in the two groups. The interval from attainment of pre-BMT complete remission to transplant was significantly longer in the MUD group. Conditioning (etoposide/total body irradiation) and graft-versus-host disease (GVHD) prophylaxis regimens were the same for all patients, and all received T cell-replete bone marrow. There was no significant difference in probability of engraftment, or time to engraftment, in the two groups. MUD BMT recipients had a significantly greater incidence of grade II-IV acute GVHD (58% versus 24% in the MRD group; P = 0.02), and demonstrated a trend towards more chronic GVHD (39% versus 15%; P = 0.06). Three years post BMT, the probabilities of transplant-related mortality were 33 +/- 11% and 20 +/- 8% in MUD and MRD groups respectively (P = 0.38); the probabilities of relapse were 28 +/- 12% and 41 +/- 9% respectively (P = 0.19). Lansky or Karnofsky performance scores in event-free survivors were 90-100 in 87% of the MUD group and 83% of the MRD group. With a median follow up of 38 months (range, 3-97), 3-year event-free survival was 49 +/- 11% and 47 +/- 9% in the MUD and MRD BMT groups respectively (P = 0.71). These results suggest that MUD BMT is a valuable therapy for children with ALL in whom BMT is indicated, and underscore the importance of efforts aimed at expediting unrelated donor searches for patients lacking a MRD.