Bone marrow transplantation (BMT) from unrelated donors (URD) is being increasingly used as a treatment modality for patients with hematological malignancy and graft failure. We hypothesized that use of unrelated donors with increased degrees of histoincompatibility, as determined by standard serological techniques, would be associated with increased difficulty in achieving engraftment and more frequent graft failure. Engraftment was analyzed in 108 patients with hematologic disease who underwent BMT from a fully serologically HLA-matched unrelated donor (n = 40) or a partially serologically HLA-matched unrelated donor (n = 68). These patients were compared with 236 patients who received BMT from matched sibling donors (MSD group) over the same time period. Primary graft failure occurred in 5% of the MSD group, 6% of the serologically matched URD group and 15% of the partially serologically matched URD group (p = 0.06). Univariate and multivariate analysis of factors relating to primary graft failure showed the only significant variable to be full or partial serological HLA-matching in the URD group. Secondary graft failure occurred in 0.7% of the MSD group, 15% of the serologically matched URD group and 25% of the partially serologically matched URD group (p < 0.0001). Univariate and multivariate analysis of secondary graft failure showed the only significant variable to be a related or unrelated donor. We conclude that primary graft failure is a significantly more frequent event in recipients of bone marrow from partially serologically matched URD than in recipients of MSD or fully serologically matched URD marrow.(ABSTRACT TRUNCATED AT 250 WORDS)