Previous investigations have defined phenotypic differences between unprimed (naive) and antigen-primed (memory) T cells from human peripheral blood. We now report that memory T cells proliferate much more than naive cells when stimulated with anti-CD3 monoclonal antibody or pairs of anti-CD2 monoclonal antibodies. Enhanced responsiveness to receptor-mediated triggering is a novel mechanism for T cells which could facilitate memory cell response to specific antigen. Furthermore, when triggered via either CD2 or CD3, memory T cells produce substantial amounts of interferon gamma while naive cells produce virtually none; this suggests that differentiation from naive to memory state is accompanied by a stable change in regulation of the gene for interferon-gamma. We conclude that naive and memory T cells are dramatically different in function as well as phenotype.