Figuring out the roles of individual cytokines can be complicated by the fact that they may share common functional subunits. Interleukin-12 (IL-12) is a heterodimer of p35 and p40 subunits, and is thought to play a key role in T-cell-dependent immunity and inflammation. In the February 13 Nature Cua et al. report that IL-23, a heterodimer of the IL-12 p40 subunit together with a distinct p19 subunit, is perhaps a more important factor in autoimmune inflammation (Nature 2003, 421:744-748). They used knockout mice, and cytokine replacement studies, to address the role of the p19, p35 or p40 subunits in experimental autoimmune encephalomyelitis (EAE), an inflammatory disease model. IL-23, but not IL-12, was essential for the development of EAE. IL-23 appears to directly activate macrophages in vivo, thereby inducing cytokine expression and late-stage inflammation.