Six patients with hematologic diseases who received bone marrow from an unrelated donor (URD) from 1992 through 1993 and survived for more than 100 days after bone marrow transplantation (BMT) were assessed for the incidence, time of onset, and extent of chronic graft-versus-host disease (cGVHD). Five patients (83%) developed cGVHD, compared with 41% of a control group consisting of 34 patients who received bone marrow from a related donor during the same period. In 4 (80%) of the 5 patients, cGVHD occurred within 70 days after BMT. This early occurrence of cGVHD was observed in only 7% of the control group (P = 0.006). cGVHD tended to involve more organs in the URD-BMT patients than in the control group. In two patients with cGVHD, an allele mismatch in HLA-DRB1 gene between the patients and donor was disclosed by DNA typing. These findings indicate that it is important to strengthen post-transplant immunosuppression, to initiate screening tests from the early post-transplant period, and to select a suitable donor matched with HLA-DRB1 alleles for the prevention of cGVHD in the URD-BMT patients.