We evaluated the outcome of two modes of T cell depletion for HLA-identical sibling stem cell transplants in 34 consecutive adult patients: group A (n = 11) received PBSC post CliniMACs immuno-magnetic enrichment of CD34(+) cells and group B (n = 23) received bone marrow following in vitro incubation with CAMPATH-1M and complement. All patients received an identical conditioning regimen which consisted of in vivoCAMPATH-1H 20 mg over 5 days, thiotepa 10 mg/kg, cyclophosphamide 120 mg/kg and 14.4 Gy TBI. No additional graft-versus-host disease prophylaxis was given. The mean T cell dose administered was 0.02 +/- 0.05 x 10(6)/kg for group A and 2.8 +/- 2.8 10(6)/kg for group B (P < 0.001). With a median follow-up of 28 months overall survival was 36.4% for group A at 12 months compared to 78.3% for group B (P = 0.001). Transplant-related mortality in group A at 12 months was 63.6% as compared to 18.0% in group B (P = 0.003). Most of the procedure-related deaths in group A occurred secondary to infection. These results suggest that extensive in vitro T cell depletion of peripheral blood stem cells in combination with in vivo T cell depletion may have profound effects upon the incidence of infections following allogeneic stem cell transplantation and this may adversely effect transplant-related mortality.