Interleukin‐1 (IL‐1) consists of two molecules, IL‐1α and IL‐1β, and IL‐1 receptor antagonist (IL‐1Ra) is a natural inhibitor of these molecules. Although the adjuvant effects of exogenously administered IL‐1 in the humoral immune response are well known, the roles of endogenous IL‐1 and the functional discrimination between IL‐1α and IL‐1β have not been elucidated completely. In this report, we investigated the role of IL‐1 in the humoral immune response using gene‐targeted mice. Both primary and secondary antibody production against T‐dependent antigen, sheep red blood cells (SRBC), was significantly reduced in IL‐1α/β^−/− mice, and was enhanced in IL‐1Ra^−/− mice. The intrinsic functions of B cells, such as antibody production against type 1 T‐independent antigen, trinitrophenyl–lipopolysaccharide and proliferative responses against mitogenic stimuli, were normal in IL‐1α/β^−/− mice. The proliferative response of T cells and cytokine production upon stimulation with anti‐CD3 monoclonal antibody were also normal, as was the phagocytotic ability of antigen‐presenting cells (APCs). However, SRBC‐specific proliferative response and cytokine production of T cells through the interaction with APCs were markedly impaired in IL‐1α/β^−/− mice, and enhanced in IL‐1Ra^−/− mice. Moreover, we show that SRBC‐specific antibody production was reduced in IL‐1β^−/− mice, but not in IL‐1α^−/− mice. These results show that endogenous IL‐1β, but not IL‐1α, is involved in T‐cell‐dependent antibody production, and IL‐1 promotes the antigen‐specific T‐cell helper function through the T‐cell–APC interaction.