From April, 1985, to February, 1989, 102 consecutive patients received unrelated donor bone marrow transplantation therapy for chronic myelogenous leukemia (CML) at four centers. Median age of the group was 31 years (range, 4.5 to 51 years). Fifty-four patients were in first chronic phase (CP) at time of transplantation, and 48 had evidence of more advanced disease (AD) (accelerated phase, 32; blast crisis, 9; second CP, 7). In 44 cases, the donor and recipient were identical at the HLA A, B, and DR loci and were nonreactive in bidirectional mixed leukocyte culture (MLC) ('matched'). In 58 cases, nonidentity between donor and recipient could be determined at at least one HLA locus or in bidirectional MLC ('mismatched'). Fifty-eight patients were prepared for transplantation with a combination of cyclophosphamide and fractionated total body irradiation (FTBI) and received acute graft-versus-host disease (GVHD) prophylaxis consisting of methotrexate alone or in combination with cyclosporine, prednisone, or antithymocyte globulin (ATG). In 44 cases, patients received preparative agents in addition to cyclophosphamide and FTBI, and marrow depleted of mature T lymphocytes by ex vivo incubation with either anti-CD3 antibody plus complement (n = 24) or Campath-1 (n = 20). Engraftment defined by a peripheral blood neutrophil count greater than 0.5 x 109/L was demonstrated in 92 cases and occurred at a median of 22 days (range, 11 to 46 days). In 10 cases, peripheral blood evidence of engraftment did not occur, and in one case, engraftment was followed by aplasia. Hematologic relapse was seen in four cases. Recurrence or persistence of the Ph1 chromosome without evidence of hematologic relapse occurred in four additional cases. The incidence of grade II to IV acute GVHD is 65% (95% confidence interval [CI], ± 10%). After adjustment for recipient age and donor matching status, recipients of T lymphocyte-depleted donor marrow had a significantly lower incidence of grade II to IV acute GVHD (P < .01); however, T depletion was not significantly associated with improved survival (P = .34), disease-free survival (P = .51), or increased incidence of relapse (P = .39). Of 102 patients, 46 are alive, with a median survival of 12 months (range, 3 to 46 months), and the Kaplan-Meier estimate of disease-free survival is 29% (95% CI, ± 9%) for the entire group at 2 1/2 years. A trend towards better disease-free survival in the 44 recipients of matched donor marrow (39%; 95% CI = ±26%) when compared with 58 recipients of mismatched marrow (27% ± 95% CI = 15%) (P = .14) was observed and could not be attributed to significant differences in recipient age, disease stage, incidence of GVHD, or failure to engraft between the two groups. Unrelated donor bone marrow transplantation provides an alternative form of curative therapy for patients with CML who do not have an HLA-matched sibling donor. Failure to engraft and a high incidence of moderate or severe acute GVHD may complicate the procedure. Efforts to delineate groups at risk for these complications and to develop innovative therapy to prevent them are warranted.