We have studied the regeneration of T cell subsets and function after BMT in 21 children affected by combined immunodeficiency after BMT. In the first months, the striking predominance of CD4+ cells displayed the primed CD45R0+ phenotype and a high number of activated (HLA-DR+) T cells were observed. Regeneration of naive CD4+ CD45RA+ cells correlated with the recovery of proliferative responses to mitogens (r= 0.64, P< 0.001). peripheral blood lymphocytes circulating after bmt undergo an increased process of in vitro cell death, resulting from two mechanisms: spontaneous apoptosis (SA), a consequence of defective production of IL-2 and down-regulation of Bcl-2 (P= 0.02 vs healthy controls), and high susceptibility to activation-induced cell death (AICD) after restimulation with mitogens. In accordance with the role of CD95/Fas in this latter process, we have observed a high level of CD95 expression (P< 0.001 vs healthy controls), correlated with AICD (P< 0.001) but not with sa, and decreasing with time after bmt (P< 0.001). both sa and aicd levels correlated with the presence of activated t cells and decreased with the progressive recovery of t cell proliferative response. therefore, the lymphocyte hyperactivated status might explain their susceptibility to apoptosis and contribute to the genesis of immunodeficiency that follows bmt.