We deliver an evidence that secretion of interleukin 1 by macrophages upon contact with T cells is an Ia-restricted and antigen-independent event. Antigen-specific T cell lines or quiescent thymocytes induce comparable quantities of IL-1 from Ia-compatible macrophages. Addition of antigen together with antigen-specific T cells does not increase production of IL-1. Con A-activated thymocyte-derived blasts induce less IL-1 than unstimulated thymocytes. Peritoneal B cells do not secrete IL-1 although they present GAT effeciently to GAT-specific T cell clones. Lastly, the production of IL-1 can be inhibited by a treatment of macrophages with monoclonal antibodies against Ia but not H-2D antigens. The results indicate that the release of IL-1 is solely a result of an interaction between Ia molecules on macrophages and the receptor for Ia on interacting T cells. This process does not require antigen/lectin bridge between the interacting cells.