Co-stimulatory signals mediated by the interaction of B7-1/B7-2 with CD28 are important for the activation of CD4+ T cells stimulated with antigen on antigen-presenting cells. There are controversies about the expression and function of B7-1/B7-2 on CD4+ T cells. The aim of this study was to analyze the expression of B7-1/B7-2 on naive and memory CD4+ T cells and the co-stimulatory function in the activation of naive CD4+ T cells stimulated by TCR ligation. Present results indicate that memory CD4+ T cells express B7-2 molecules on their surface, whereas naive CD4+ T cells do not. Neither memory nor naive CD4+ T cells expressed B7-1 molecule on their surface, although B7-1 mRNA was faintly expressed in memory T cells. B7-2 molecules expressed on memory T cells co-stimulated CD4+ naive T cells stimulated with plate-coated anti-CD3 to produce IL-2. Naive CD4+ T cells were shown to express B7-2 after co-stimulation with B7-2 and TCR ligation, because the naive T cells stimulated with anti-CD3 and B7-2CHO expressed B7-2 on their surface, although it remained to be studied whether the co-stimulation with B7-2 directly induced B7-2 expression on naive T cells. Our present results indicate that memory CD4+ T cells play some role in the activation of naive CD4+ T cells through the co-stimulation with B7-2 molecules.