Effects of vasoactive intestinal peptide (VIP) on superoxide anion (O2-) formation by N-formyl-methionyl-leucyl-phenylalanine (fMLP)-activated inflammatory cells from healthy volunteers were investigated using 2-methyl-6-[p-methoxyphenyl]-3,7-dihydroimidazo [1,2-a]pyrazin-3-one (MCLA) as a chemiluminescence probe. VIP inhibited the maximal light intensity of MCLA-dependent luminescence in a dose-dependent manner by the activated peripheral blood neutrophils, mononuclear cells and also by the human monoblast cell line U937, the capacity of which for O2- formation was induced by pretreatment with interferon-gamma. 3 x 10(-6) M VIP also inhibited O2- formation by the activated peripheral blood eosinophils and alveolar macrophages obtained by bronchoalveolar lavage.