We retrospectively analyzed 83 consecutive recipients of donor lymphocyte infusions (DLI) after allogeneic transplantation for factors associated with disease response and graft-versus-host disease (GVHD). DLI was highly effective in relapsed chronic phase chronic myeloid leukemia (CML), with 71% of patients achieving durable complete remissions (CR). In relapsed acute myeloid leukemia, DLI led to durable CRs in 31% of patients; the rate was <20% in all other diseases. Achieving full donor chimerism and GVHD were predictive of CR. Grade II or higher acute or chronic GVHD occurred in 36 (43%) patients and contributed to death in 13 (16%). Even more patients, 33 (40%), died of their underlying malignancy, including 10 who developed active GVHD. In relapsed CML, most durable CRs occurred without clinically apparent GVHD, yet all responders achieved full donor chimerism, including 6 with coincident normal host hematopoiesis at the time of DLI. Thus, in CML, potent lymphohematopoietic graft-versus-host reactions occurred even in the absence of clinically apparent GVHD; this confirms the ability to dissociate these processes and argues against a leukemia-specific immunologic effect. DLI clearly has efficacy in the treatment of relapsed disease after allogeneic transplantation. However, with the exception of CML, most patients die of their underlying disease because of insufficient antitumor activity even with active GVHD.