Twenty-two multi-transfused patients with a long duration of severe aplastic anemia (SAA) received a transplant from an HLA-matched donor after cyclophosphamide (CY) plus antithymocyte globulin plus procarbazine using CD34+ enriched blood stem cells + fresh marrow. Peripheral blood stem cells (PBSC) were collected on days 5 and 6 of G-CSF (10 μg/kg/day), and T cells were depleted using an immunoadsorption column (n = 15) or magnetic cell sorting (n = 7). Marrow harvesting was performed 48 hr after the last leukapheresis. Two patients (9.1%) that developed graft failure had a successful engraftment again using unpurged PBSC. Median time to neutrophils ≥0.5 × 109/l and platelets ≥20 × 109/l without platelet transfusions were 12 days and 17 days, respectively. Acute graft-versus-host disease (GVHD) grade II occurred in four of 22 patients. No patient developed grade III or IV acute GVHD. Four of the evaluable 21 patients had chronic GVHD. One patient developed extensive disease. Three patients (13.6%) died from CY-induced heart failure, extensive-type chronic GVHD, and sepsis of unknown cause. The Kaplan–Meier estimate of survival was 83.9% (95% CI, 70.1–95.2%) with a median follow-up duration of 33.5 (6–44) months. CD34+-enriched PBSC in combination with unmanipulated marrow seem to play a role in overcoming the sensitization to histocompatibility antigens without an apparent increase in GVHD. The stem cell component therapy may be feasible for the high-risk SAA adult patients. Am. J. Hematol. 69:15–22, 2002. © 2002 Wiley-Liss, Inc.