Our group has investigated the hormonal regulation of body fat mass. Specifically, we have investigated the role of interleukin-6 (IL-6), and IL-1 in the regulation of body fat. Circulating IL-6, in the absence of heavy exercise and inflammation, is to a large extent is produced by adipose tissue. Using knockout mouse models, we have obtained evidence that both endogenous IL-6 and IL-1 suppresses fat mass and prevents mature-onset obesity. There are also data indicating that combined IL-6 and IL-1 deficiency causes early onset severe obesity. Both IL-6 and IL-1 exert their major anti-obesity effects at the level of the CNS, presumably the hypothalamus. Studies in humans indicated that polymorphisms of IL-6 and IL-1 system genes are associated with differences in body fat mass. For instance, the results of several studies show that the “weak” IL-6 -174C IL-6 gene promoter variant is associated with both decreased IL-6 production and obesity. Consequently, IL-6, IL-1 , and possibly also other parts of the immune system are important for regulation of fat mass in experimental animals and humans.