The effect of recombinant human interleukin-2 (rhIL-2) and recombinant human interferon-gamma (rhIFN-gamma) were evaluated on superoxide (O2-) production of human polymorphonuclear neutrophils (PMNs). Ten minutes incubation with rhIL-2 showed a dose-dependent enhancement of n-formyl-methionyl-leucyl-phenylalanine (FMLP)-induced O2-production of human PMNs, and the rate of enhancement reached 49.6% at the concentration of 3000 U/ml rhIL-2. Same pretreatment with rhIFN-gamma also showed a dose-dependent enhancement of FMLP-induced O2-production of human PMNs, and the maximal rate of enhancement was 47.0% at the concentration of 3000 U/ml rhIFN-gamma. Any cytokines given alone did not induce O2- production. These cytokines showed no enhancement of phorbol myristate acetate (PMA)-induced O2- production, neither. The effects of these cytokines to FMLP-induced O2- production were kept in calcium-free medium. Moreover, incubation with these cytokines caused no elevation of intracellular free calcium concentration [( Ca++]i) in resting PMNs. Incubation with them did not change the increase of [( Ca++]i) of PMNs induced by FMLP significantly, neither. Recombinant forms of cytokines are used clinically, now. These results may be helpful for the use of them.