The graft-versus-myeloma (GVM) effect of donor lymphocyte infusions (DLIs) is well established. We now report the outcome of DLI in 54 patients with relapsed myeloma following allogeneic transplantation. Twenty-eight patients (52%) responded, 19 patients (35%) with a partial response and 9 patients (17%) with a complete response. Progression-free and overall survival were 19 and 23 months, respectively. We found that acute and chronic graft-versus-host disease (GVHD) observed in 57% and 47% of patients, respectively, following DLI were the strongest predictors for response. This suggests that targets for GVHD and GVM are identical. In a subgroup analysis, deletion of chromosome 13, as determined by double-color fluorescence in situ hybridization (FISH), had no impact on outcome, indicating that these patients are candidates for early allogeneic transplantation followed by DLI, in case of insufficient response.