CD30 is well recognized as a marker expressed by a heterogeneous group of lymphomas and in several immune and autoimmune disorders. However, the function of CD30 in theses diseases or in the normal immune response has remained unclear. Studying gene expression patterns induced by stimulating CD30 signals on a large granular lymphoma cell line, YT, with an agonistic anti-CD30 antibody, we found that CD30 signals affected proapoptotic and antiapoptotic genes, regulated cytotoxicity, and controlled molecules regulating T cell traffic. Creating CD30-L deficient mice and studying CD8 CTL activation and memory responses, it was observed that the absence of CD30-L resulted in diminished primary clonal expansion of CD8 cells. In addition the absence of CD30-L abolished clonal contraction after primary expansion and interfered with secondary expansion upon boosting. The studies suggest that CD30 regulates CD8 CTL function and survival during memory responses and is important for clonal contraction.