Large granular lymphocytes (LGL) share phenotypic and functional properties with monocytes. We have investigated the production of procoagulant activity (PCA), so far attributed to cells of the monocyte-macrophage lineage, by LGL. Endotoxin triggered interleukin (IL-1) release and PCA activity by highly purified monocyte preparations. In contrast, LGL exposed to endotoxin produced IL-1 but had no PCA activity. Similarly ineffective in inducing PCA in LGL were other stimuli that either triggered monocyte PCA or stimulated the natural killer cytotoxicity of LGL. Thus, although LGL share properties with monocytes such as the capacity to produce IL-1, PCA is confined, among circulating leukocytes, to cells of the monocyte lineage.