Over the past 25 years there has been an ever-expanding interest in the mediators that control the immune response [98,133], One of these is produced by macrophages and was first called “lymphocyte activating factor” [49–51] but is now designated “interleukin-1” (IL-1) [118]. As the physical characteristics of IL-1 began to be described, it was noted that they were similar to those of endogenous pyrogen (EP) [128] [151] and leukocytic endogenous mediator (LEM) [85]. Since then, many of the biochemical changes that occur in the host during infection, inflammation, or neoplasia have been attributed to this unique family of monokines. In this review, the family of monokines that has similar physical and biological properties will be referred to as EP/LEM/IL-1. When only one biological activity was measured, the designation will be for that activity. It will be the purpose of this review to examine the evidence that suggests that EP/ LEM/IL-1 has numerous biological activites and to describe its chemical and biological properties, species specificity, and possible sites of action. Finally, I will attempt to address the issue of why there might be a closely related group of mediators with such a broad range of biological activities.