The polypeptide interleukin-1 mediates many host responses to infection and inflammation. A method was developed for studying interleukin-1 levels in human plasma from febrile patients. Interleukin-1 activity was also consistently found in plasma samples from women in the luteal phase of their menstrual cycle. This activity was neutralized by a specific antiserum to human interleukin-1 and was low in plasma from healthy men and preovulatory women. Thus interleukin-1 appears to have a role in normal physiological conditions as well as in disease states.