Our present understanding of the pathogenesis of fever is that host macrophages, following activation by an appropriate stimulus such as Gram-negative lipopolysaccharide (LPS) immune complexes, or primed lymphocytes in the presence of specific antigen, synthesize and release endogenous pyrogen (EP). EP is carried in the blood circulation to the hypothalamic area of the brain where its action, involving a protein synthetic step, results in an increase of the level at which body temperature is maintained. Recently, it was shown that EP is very similar and possibly identical to another macrophage mediator previously called lymphocyte activating factor and now known as interleukin-1 (IL-1) which, in conjunction with lectin or specific antigen, induces clonal expansion of T lymphocytes. We show here that murine T-cell proliferation in response to IL-1 in vitro is greatly increased when the cells are exposed to a temperature typical of fever and that injection of the same IL-1 causes fever in mice. If this relationship exists in vivo, the resulting facilitation of a T-cell-dependent immune response may well confer survival value and contribute to the evolutionary conservation of fever--a phylogenetically ancient response to infection.