The effect of N-acetylcysteine (NAC) on human neutrophil and monocyte cell viability, chemotaxis, oxygen consumption and chemiluminescence was studied. It was found that NAC at concentrations higher than 3 X 10(-2) M resulted in neutrophil and monocyte cytotoxicity. The studies on the effect of NAC on neutrophil and monocyte chemotaxis showed that NAC inhibited chemotaxis of both cell types in a concentration dependent manner. NAC at 3 X 10(-2) M inhibited chemotaxis of both cell types by about 50% and at 10(-1) M inhibited PMN chemotaxis by 95% and MNL chemotaxis by 85%. The studies on the effect of NAC on neutrophil chemiluminescence demonstrated that NAC at concentrations of 1.5 X 10(-2) M, or higher, inhibited the response of the activated cells totally. When pH adjusted NAC or Mucomyst was used the inhibition was observed with higher concentrations of the drug (1.5 X 10(-1) M). NAC exhibited a similar pattern of inhibition on monocyte chemiluminescence response. These findings demonstrate that NAC, at concentrations obtainable in vivo by inhalation, impairs the chemotaxis and generation of oxygen radicals by human phagocytic cells. This property of NAC could have important implications concerning the prevention of tissue damage caused by these cells in inflammatory areas.