Previous studies have demonstrated that the treatment of neutrophils with proteolytic enzymes markedly reduces the expression of receptor III for the Fc portion of IgG (Fc gamma RIII), but it does not affect the number of Fc gamma RII on the cell surface. In the present study, we analysed the effect of proteolytic enzymes on functional responses of neutrophils induced by immune complexes (IC). Our results showed that treatment with pronase or chymotrypsin markedly increased the binding of IgG-coated erythrocytes (IgG-E) to neutrophils, as well as their capability to display IgG-mediated functions such as antibody-dependent cellular cytotoxicity (ADCC) and chemiluminescence (CL) induced by IgG-E, responses that have been shown to be completely dependent on Fc gamma RII. A similar enhancing effect was observed, in all cases, after neutrophil treatment with neuroaminidase. We also studied the effect of proteolysis on neutrophil activation induced by other types of IC. It was found that pronase and chymotrypsin significantly enhanced CL responses induced by soluble IC (sIC) but did not modify the responses induced by either precipitating IC (pIC) or soluble IC prepared with cationized antibodies (catIC). On the other hand, neuroaminidase significantly enhanced CL induced by either sIC, pIC or catIC. Taken together, our data suggest that the activity of Fc gamma RII can be up-regulated by proteolysis. However, this effect appears to be strongly dependent on the characteristics of the IC employed as stimulus.