Systemically administered lipopolysaccharide (LPS) elicits profound changes in pituitary hormone secretion. Pro-inflammatory cytokines have been proposed as mediators of these responses. In this study, we used in-situ hybridization histochemistry to investigate LPS-induced cytokine gene expression in the rat pituitary. After i.p. or i.v. injection of various doses of LPS, mRNA for the immediate-early gene IkappaBu (an inhibitor of NF-kappaB, a transcription factor that regulates the expression of many pro-inflammatory cytokines) was induced in the anterior lobe as early as 0.5 h. The induced IkappaBalpha mRNA expression peaked at 1 h. In the posterior lobe, IkappaBalpha mRNA was first induced at 0.5 h and peaked at 2 h. A similar spatiotemporal pattern of interleukin-1b (IL-1) mRNA induction was observed. In addition, at 2 h after injection, TNFalpha, IL-1beta converting enzyme (ICE), and IL-1 receptor antagonist (IL-1RA) mRNAs were induced in both anterior and posterior lobes. Type 1 IL-1 receptor (IL-1R1) mRNA was constitutively expressed in the pituitary, and its expression level did not change after the LPS injection. Interestingly, the mRNA coding for glial fibrillary acidic protein (GFAP), an astrocyte marker, was selectively induced in the posterior lobe at 2 h after LPS injection, suggesting that LPS affects pituicyte function. Together, these results suggest that LPS acts directly on the pituitary to rapidly induce cytokine expression. Locally synthesized cytokines may activate cytokine receptor bearing cells to modulate the endocrine activities of the pituitary.