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 (γ(c)) might contribute to this abnormality. The γ(c) expression on peripheral blood mononuclear cells was analyzed by flow cytometry using a monoclonal antibody to γ(c). IL-4 binding in association with γ(c) expression was assessed using biotinylated IL-4 in two-color flow cytometry. Mean fluorescence of γ(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 γ(c) down-regulation was confirmed using the in vitro stimulated donor cells. In the same system it was shown that down-regulation of γ(c) is accompanied by decreased numbers of IL-4 binding cells. In conclusion, a decreased expression of the γ(c) on peripheral blood mononuclear cells from CD patients with active disease might have an important pathogenetic significance in this chronic intestinal disorder.