Tumor necrosis factor alpha (TNF-alpha) is an important mediator in many pathophysiologic processes, both in the central nervous system (CNS) and in the periphery. For this study, we have designed a very sensitive immuno-PCR detection system to investigate the time course of TNF-alpha induction in the rat cerebrospinal fluid after intracerebroventricular administration of bacterial lipopolysaccharide (LPS). Immuno-PCR combines antibody specificity with PCR signal amplification and provides a sensitivity in the picomolar range. The enhanced sensitivity of this assay allowed the detection of TNF-alpha in the cerebrospinal fluid as early as 15 min after intracerebroventricular administration of LPS. The present results suggest that the ventricular compartment of the CNS, although confined within the blood-brain barrier, is highly responsive to proinflammatory stimuli such as LPS administration. Insight into the molecular mechanisms underlying this compartmentalization could be key to the pathology and treatment of many CNS diseases, especially the meningitides.