Peripheral blood stem cell (PBSC) transplants may be depleted of lymphoid progenitors, thereby disabling the cellular immune response against viral pathogens after autologous PBSC transplantation (PBSCT). To monitor the cellular immune reconstitution after autologous PBSCT, we investigated the cytolytic activity (CLA) of peripheral blood T lymphocytes against Epstein-Barr virus (EBV) in 13 patients with non-Hodgkin's lymphoma or multiple myeloma. The individual EBV-directed CLA (EBV-CLA) was determined by calculating the number of cytolytic effector cells in 106 T cells needed to lyse 25% of autologous EBV-transformed B-lymphoblastoid cells, expressed as lytic units (LU25). During the first 6 months after PBSCT, the EBV-CLA was only 14.6% of the response of healthy controls (median 4. 8 vs. 32.9 LU25). Thereafter, the EBV-CLA increased to 28.15 LU25 (median) or 86% of healthy controls. Monthly follow-up analyses in five selected patients showed that the EBV-CLA was barely detectable at 4 weeks and recovered at 8-12 weeks after PBSCT in four out of five patients. Effector cells consisted mostly of CD8-positive T lymphocytes, with small CD4- and CD3/CD56-positive lymphocyte fractions. These results suggest that the reconstitution of the cellular immune response against EBV takes 8-12 weeks after autologous PBSCT.