Soybean trypsin inhibitor (SBTI) shares some structural homology with interleukin-1 (IL-1) and was tested for IL-1 bioactivity. Human T-cells proliferated maximally when stimulated with PMA and SBTI but failed to respond to either stimulus alone. This response was abrogated by neutralizing antibodies to IL-1 beta but not to IL-1 alpha. However, immunoblots showed no cross-reactivity between SBTI and anti-IL-1 antibodies. Furthermore, SBTI did not bind to IL-1 receptors on YT cells and did not activate a murine T-lymphoma or human T-hybridoma. Supernantants from monocytes stimulated with SBTI contained significant levels of IL-1 activity. The data show that SBTI has no direct IL-1 activity but can stimulate T-cells indirectly through an IL-1 dependent mechanism.