The cytokine network is an important homeostatic system with potent activities in immune surveillance, growth, developmental and repair processes. Although interleukin-1beta (IL-1beta) is considered a pivotal pro-inflammatory cytokine, merely focussing on its inflammatory role would be too narrow an approach. Elucidation of the human, the mouse and the Fugu rubripes (pufferfish) genome now enables a more comprehensive overview of this cytokine family and its receptors in several vertebrate classes. Phylogenetic analyses of the IL-1 family members, comprising over 80 sequences of various fish, amphibian, avian and mammalian species, reveal that for only a few mammalian IL-1 family members unambiguous orthologues have been found in fish, indicating a recent origin of some of the mammalian IL-1 family members. Interestingly, the Fugu genome did reveal teleost orthologues for IL-18 and its putative receptor complex. All teleost IL-1beta sequences cluster separately from IL-1beta sequences of other species. In contrast, a number of IL-1 receptor family members have well conserved fish orthologues. This supports the concept of an ancestral role of this family, possibly in the brain.