Nineteen adult patients with poor-risk hematologic malignancy received T cell-depleted (TCD) hematopoietic progenitor cell (HPC) transplant from partially mismatched related donors (PMRD). The preparative regimen (FITFA) included fractionated TBI, thiotepa, fludarabine, and horse (n = 3) or rabbit (n = 16) anti-thymocyte anti-sera (ATG). GVHD prophylaxis consisted of TCD by positive/negative selection using the Isolex 300i system and pre-transplant ATG with no post-transplant immunosuppression. The mean number (+/-s.d.) of transplanted CD34(+) and CD3(+) cells were 8.9 x 10(6)/kg +/-4.3 (range 2.6-19.3) and 1.4 x 10(4)/kg +/-1.2 (range 0.3-4.6) respectively. Seventeen patients evaluable for neutrophil engraftment achieved an ANC >0.5 x 10(9)/l at a median of 12 days (range 9-27), with evidence of full donor chimerism. Thirteen patients died of the following causes: relapse (n = 6), infections (n = 5), interstitial pneumonia (n = 1), and unknown causes (n = 1) None of the recipients of rabbit ATG required therapy for acute or chronic GVHD. Five patients are alive and disease-free at a median time of 303 days post transplant (range 100-660). The FITFA preparative regimen using fractionated TBI is well tolerated and is sufficiently immunosuppressive to allow rapid and stable donor origin hematopoietic engraftment without 'mega' doses of CD34(+) cells. Combination of stringent ex vivo TCD and pre-transplant ATG is effective GVHD prophylaxis.