The aim of this work was to analyze the implication of IL-4 in the antibody response induced in vivo after immunization with a class II T-cell-independent (TI) antigen. IL-4 suppression, through administration of a rat monoclonal antibody antimurine IL-4 (11B11), in euthymic BALB/c mice during the course of immunization with the DNP-coupled hydroxyethyl starch (TI antigen), inhibited the production of anti-DNP IgG1 antibodies, potentiated the synthesis of IgG2a and had no effect on the other isotypes (IgM, IgG2b and IgG3). After IL-4 treatment of athymic BALB/c mice in the same conditions, although the IgG2a production was not increased, the IgG1 synthesis was significantly decreased, as was observed in euthymic mice. These results demonstrate that cytokine IL-4 plays an active role in vivo in the regulation of antibody response after immunization by a T-cell-independent antigen, in normal as well as in nude mice. The origin of IL-4 in these animals and especially in those athymic mice remains to be determined.