The ultimate fate of T cells undergoing antigen-induced cell death in vivo remains controversial. Whereas apoptosis of CD4+ T cells driven by superantigen is readily detectable in lymphoid organs, CD8+ T cells have been reported to disappear from the lymphoid organs and accumulate in the liver where they undergo apoptosis. Using transgenic mice that produce large numbers of ovalbumin-specific CD8+ T cells (OT-I cells), we were able to investigate the events that follow soluble peptide administration in an independent CD8+ T cell system. Here we show that the OT-I cells undergo proliferation and apoptosis in situ in lymphoid organs in response to antigenic stimulation with no evidence for liver involvement. This is similar to the course of events found for CD4+ T cell activation and counters the view that the liver is a general site for CD8+ T cell clearance following antigen-specific activation.