Blood mononuclear cells from newborns and from adults, immune or nonimmune to herpes simplex virus, were cultured with IL 2 and herpes simplex virus and the amount of γ-interferon in the supernatant measured after 3 days. The newborn and nonimmune adult cells made equivalent trace amounts of γ-interferon in cultures containing either herpes simplex virus or IL 2 alone and there was a 5- to 10-fold increase in cultures containing both. Experiments in which the Leu 11+cells were either depleted or enriched suggest that this subset of natural killer cells is both necessary and sufficient for γ-interferon production in the absence of immune T cells.