Interleukin-2 (IL-2) exercises an array of biological effects on many cells including the functional activation of cells of the innate immune response. Heterophils, the avian equivalent of the neutrophil, function as professional phagocytes to aid in regulation of innate host defenses. The objective of the present studies was to examine the effects of recombinant chicken IL-2 (rChIL-2) on functional activities of heterophils from chickens during the first 3 weeks after hatch. Peripheral blood heterophils were isolated and incubated with either COS cell-derived rChIL-2 or supernatants from mock-transfected COS cells. rChIL-2 had no effect on the functional activities of heterophils from day-of-hatch chickens, but significantly increased the phagocytosis and bactericidal activity of heterophils from 7- and 14-day-old chickens. rChIL-2 induced no direct stimulation of the respiratory burst by heterophils, but primed heterophils from 7- and 14-day-old birds for an enhanced respiratory burst in response to phorbol ester stimulation. Lastly, rChIL-2 had neither direct nor priming effects on heterophil degranulation. The enhancing effects on heterophil functional activity by rChIL-2 were abated by a neutralizing anti-chicken IL-2 mAb and were therefore specific for this cytokine. These results show that rChIL-2 can directly activate chicken heterophils to exert effector functions, and that heterophil activation by rChIL-2 is also an age-dependent event.