We examined the developmental profile of TCR-gamma/delta+ cells with respect to CD45RO expression. Although total TCR-gamma/delta+ cells were negligible in the neonatal blood and increased with advancing age, most blood TCR-gamma/delta+ cells markedly expressed CD45RO without a distinction of age, probably reflecting a different CD45RO expression of two subsets defined by BB3 and delta TCS1 mAbs. The vast majority of BB3+ cells expressed CD45RO, whereas expression of CD45RO was virtually absent in the delta TCS1+ population. Functional studies revealed that, while both TCR-gamma/delta+ cell subsets showed CD3-mediated activation, only BB3+ (or Ti gamma A+) cells, but not delta TCS1+ cells, appeared to proliferate in response to PPD in PPD-reactive individuals. The results suggested that the CD45RO+ (BB3+ or Ti gamma A+) subset among blood TCR-gamma/delta+ cells may be mainly involved in the memory or primed component of the immune system responding to some foreign antigens.