The ontogeny of the human immune system was studied by analyzing fetal and adult tissues for the presence of various lymphocyte populations and activation/maturation markers. CD95 (fas) was expressed in hematopoietic tissues during the final stages of development of monocytes, granulocytes, NK cells and T cells, but to a much lesser extent on B cells. In the periphery, CD95 expression declined on granulocytes and NK cells. CD95 was expressed at a higher level on CD45RA(+) peripheral T-cells in the fetus than in the adult. Contrary to the belief that most fetal T-cells are naive or resting, a notable number of CD45RO(+) T-cells were observed as well as an unique CD95(-)CD45RO(+) population. Activation markers CD25, CD122, CD69 and CD80 were also present on fetal T-cells. These findings indicate that in the initial weeks following thymic maturation, a high frequency of T-cells is activated in the periphery of the fetus. (C) 2003 Elsevier Science Ltd. All rights reserved.