alpha 1-Acid glycoprotein (alpha 1-AGP), a naturally occurring human plasma protein and acute-phase reactant, was extracted by a two-step procedure from sera collected from four healthy men. Its activity was tested in vitro on human polymorphonuclear (PMN) functions (migration, aggregation, O2- generation). alpha 1-AGP was not chemoattractant but inhibited the PMN response to the chemoattractant formylmethionyl-leucyl-phenylalanine without affecting spontaneous migration (Boyden and agarose methods of assessment). At concentrations between 0.15 and 0.45 mg/ml, alpha 1-AGP exerted an aggregating effect with a maximal effective concentration of 0.3 mg/ml. alpha 1-AGP inhibited superoxide generation by PMNs stimulated either by opsonized zymosan or phorbol myristate acetate. This inhibition varied according to the intensity of the stimulation. At low stimulus concentrations, a dose-dependent inhibition of membrane-associated PMN responsiveness to soluble or particulate stimuli was observed. These findings suggest that alpha 1-AGP may be able to prevent PMN activation in the course of inflammatory processes in vivo.