STATs (signal transducers and activators of transcription) efficiently carry information from cell surface cytokine receptors (which cause STAT phosphorylation) to the nucleus (where STATs work as transcriptional activators). Yuan et al. (see the Perspective by O'Shea et al.) report that Stat3 is also regulated by acetylation of a specific lysine residue. Stat3 is associated with the transcriptional coactivators CBP and p300, which have histone acetyltransferase activity and can modify Stat3 in vitro. Acetylation of the key lysine residue appears to be required for dimerization of Stat3 and for transcriptional activation of genes in cells treated with the cytokine oncostatin M. Cells expressing a mutant form of Stat3 that is not acetylated were insensitive to gene regulation and growth promotion by oncostatin M.