The hepatic acute phase response (APR) is a reproducible alteration in a specific set of proteins synthesized by the liver. Tissue injury produces a cascade of cytokine mediators which, in combination with other factors(including glucocorticoids), alters APR gene expression following an inflammatory stimulus. Interleukin-6, a major component of this cascade, activates latent cytoplasmic transcription factors (STAT proteins). We hypothesized that the hepatic APR following inflammation induced by turpentine injection would include rapid activation of STAT proteins. Hepatic nuclei from adult male rats treated with s.q. turpentine were isolated at varying time points after treatment and nuclear protein extracts were prepared. Binding of STAT proteins was examined using labeled DNA oligonucleotides containing known STAT binding sites in electromobility shift assays (EMSA). Identity of the various STAT proteins observed in these extracts was assessed by addition of antibodies to specific known STAT proteins with observation of altered mobility in EMSA (supershift assay). We found that only Stat3 and not Stats 1 or 5 is activated after turpentine inflammation. This response is present within 2 hr of turpentine treatment and is not altered by pituitary ablation. We conclude that the inflammatory response induced by turpentine injection results in rapid and specific activation of Stat3, but not other STAT proteins, and is pituitary independent.