Interleukin (IL) 4 is a type 2 cytokine which has a negative immunoregulatory role in human infection. IL-4 suppresses the production of interferon-gamma and enhances IL-10 synthesis. However, the effect of IL-4 on proliferative response of lymphocytes remains to be elucidated. We have previously reported an increase in production of IL-4 in subjects with Helicobacter pylori (H. pylori) infection. To evaluate whether the increased IL-4 is responsible for the down-regulation of immune responses in H. pylori infection, we observed the proliferative response of peripheral blood lymphocytes (PBL) co-cultured with phythaemagglutinin (PHA) or H. pylori in the presence and absence of added IL-4. As we have previously shown, PHA and H. pylori may increase PBL proliferation (P < 0.001). An increase in PBL proliferation was observed when PBL were co-cultured with PHA (P < 0.001) or H. pylori (P < 0.001) in the presence of IL-4 compared to that in the absence of IL-4. The optimal dose of IL-4 to give maximal lymphocyte proliferation is 50 pg/ml for the PHA-stimulated group or 100 pg/ml for the H. pylori-stimulated group. The data suggest that the increased IL-4 does not directly contribute to suppressed lymphocyte proliferation in H. pylori infection. Further studies will be required to determine the role of IL-4 in other aspects of down-regulation of immune responses in H. pylori infection.