Mononuclear cell proliferative response to IL-2 and functional response to IL-4 is disturbed in IBD. The aim of the present study was to verify whether altered expression of the common gamma chain (gamma c) might contribute to this abnormality. The gamma c expression on peripheral blood mononuclear cells was analyzed by flow cytometry using a monoclonal antibody to gamma c. IL-4 binding in association with gamma c expression was assessed using biotinylated IL-4 in two-color flow cytometry. Mean fluorescence of gamma c expression was significantly decreased in active CD patients as compared to inactive CD and healthy controls (P < 0.05). Cell activation as a possible reason for gamma c down-regulation was confirmed using the in vitro stimulated donor cells. In the same system it was shown that down-regulation of gamma c is accompanied by decreased numbers of IL-4 binding cells. In conclusion, a decreased expression of the gamma c on peripheral blood mononuclear cells from CD patients with active disease might have an important pathogenetic significance in this chronic intestinal disorder.