The cytomegalovirus (CMV)-specific CD8+ cytotoxic T-lymphocyte (CTL) and CD4+ T-helper cell (Th) functions were characterized in 15 CMV seropositive recipients of autologous peripheral blood stem cell or bone marrow transplants. These immune functions were evaluated in peripheral blood specimens obtained before and at 1, 2, and 3 months after transplant. For study of CTL activity, blood mononuclear cells were cocultured with CMV-infected autologous fibroblasts for 2 weeks and then tested for cytotoxicity against CMV-infected or mock-infected autologous and HLA-mismatched fibroblasts. The Th response to CMV antigen was assessed by standard lymphoproliferative assay. CMV-specific CD8+ CTL and CD4+ Th responses were detectable in 12 (80%) and 14 (93%) patients, respectively, in the first 3 months after transplantation. A Th response to CMV was always present by the time of first CTL detection. During the posttransplant period, CMV infection occurred in 6 (40%) patients, and detection of CMV-specific CD8+ CTL activity was associated with protection from subsequent CMV infection (P = .002). Among CMV seropositive autograft recipients, CMV-specific CD8+ CTL and CD4+ Th responses are restored in a large proportion of patients in the first 3 months after transplantation, and the presence of a specific CD8+ CTL activity affords protection from CMV infection.