We have studied the activation of signal transducers and activators of transcription (STATs) in trigeminal ganglion after intraperitoneal injection of lipopolysaccharide (LPS) and Interleukin-1beta (IL-1beta). Using electrophoretic mobility shift assays we have shown that STAT1 and STAT3 are activated within 1 to 2 h. of injection of either LPS or IL-1beta. Eight hours after LPS injection the DNA binding activity of these complexes is still elevated while induction by IL-1beta returns to baseline levels within 4 h. By immunohistochemistry, using an antibody specific for the tyrosine phosphorylated, activated form of STAT-1, we show that this induction occurs in sensory neurons. IL-6 may be important in this cascade since induction of STATs by IL-1beta is blocked in Interleukin-6 knock out mice.