The cytotoxicity of natural killer (NK) cells against X562 cells and their responsiveness to interferonα and interleukin 2 (IL-2) were studied throughout child-hood using51Cr-release and single-cell assays. Although NK activity was extremely low in the neonatal period, it almost reached the adult level during 1 to 5 mo of age and remained at that level thereafter. At the single-cell level, the binding, lytic, and recycling abilities were also depressed in the neonatal period, but these abilities improved conspicuously after this period; in particular, the lysis and recycling were at higher levels during 6 mo to 4 y of age. The absolute numbers of circulating cytotoxic NK cells were high during infancy to early childhood: they were 54 \pm 24 (mean \pm SD/mm3) in neonates, 115 \pm 48 in 1− to 5-mo-old infants, 121 \pm 42 in 6− to 12-mo-old infants, 93 \pm 26 in 1− to 4-y-old children, and 42 \pm 16 in adults. Inter feron-α and IL-2 could enhance NK activity throughout childhood. The IL-2 enhancement was prominent especially in the neonatal period; IL-2 yielded a 2.5-fold in crease in the number of cytotoxic cells and improved the recycling to the adult level. At older ages, interferon-α and IL-2 yielded 1.4-and 1.9-fold increases in the number of eytotoxic cells, respecively, but did not enhance the recycling. The iacreased number of NK cells with adequate cytotoxic abilities during infancy to early childhood indicates the predominance of NK immunity during these periods. IL-2 is a cytokine that induces high levels of NK cytotoxicity even in neonates. (Pediatr Res28: 316–322, 1990)