Inflammatory responses are strictly regulated by coordination of pro-inflammatory and anti-inflammatory mediators. Interleukin-4 (IL-4) and interleukin-10 (IL-10) have typically the biologic anti-inflammatory effects on monocytes, but uncertain effects on polymorphonuclear leukocytes (PMNs). The PMNs are the first line of cellular response for host defense during acute inflammation. To modify hyper-inflammatory reaction with biologic anti-inflammatory mediators, we have determined the biologic anti-inflammatory activities of IL-4 and IL-10 on human PMNs. Human PMNs were pretreated with IL-4 or IL-10 and then stimulated with formyl methionyl leucyl phenylalanine (fMLP) for times indicated. The level of H2O2, interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) were determined in the each cell free supernatants. fMLP plays the role of a typical pro-inflammatory agent and, at least in determined conditions, down-regulated TNF release. IL-4 acts as an anti-inflammatory mediator but IL-10 did not show its anti-inflammatory activities on fMLP-stimulated human PMNs. IL-4 and IL-10 have different anti-inflammatory mechanisms. Perhaps, IL-10 needs co-factors to act as an anti-inflammatory mediator.