To determine whether viral antigens associated with infected cells were processed for presentation to T cells, we cultured human blood mononuclear cells (MNC) from varicella-zoster virus (VZV) immune donors with VZV-infected fibroblasts of known HLA type which had been fixed in 0.05% glutaraldehyde. After 7-8 days of culture thymidine uptake by T4+ cells exceeded that of T8+ cells. Stimulated cells were depleted of adherent cells and restimulated with VZV-infected fibroblasts from donors matched or unmatched with the responder for HLA type in the presence or absence of fresh adherent cells. Proliferation of the VZV-specific blasts required the presence of adherent cells matched with the responder lymphocytes for HLA-DR; conversely, the VZV specific response was not restricted by the MHC of the fibroblasts used in the restimulation assay. Preincubation of the adherent cells with chloroquine inhibited the proliferative response in a dose-dependent manner. These results suggest that VZV antigens on infected cells may be processed by monocytes for presentation to T cells.