We examined the developmental profile of TCR-γ/δ+ cells with respect to CD45RO expression. Although total TCR-γ/δ+ cells were negligible in the neonatal blood and increased with advancing age, most blood TCR-γ/δ+ cells markedly expressed CD45RO without a distinction of age, probably reflecting a different CD45RO expression of two subsets defined by BB3 and δTCS1 mAbs. The vast majority of BB3+ cells expressed CD45RO, whereas expression of CD45RO was virtually absent in the δTCS1+ population. Functional studies revealed that, while both TCR-γ/δ+ cell subsets showed CD3-mediated activation, only BB3+ (or TiγA+) cells, but not δTCS1+ cells, appeared to proliferate in response to PPD in PPD-reactive individuals. The results suggested that the CD45RO+ (BB3+ or TiγA+) subset among blood TCR-γ/δ+ cells may be mainly involved in the memory or primed component of the immune system responding to some foreign antigens.