Central nervous system (CNS) inflammation in cases such as head trauma, infection and stroke has been associated with the occurrence of epileptic seizures. Microglia, the principal immune cells in the brain, readily become activated in response to injury, infection or inflammation. The bacterial endotoxin lipopolysaccharide (LPS) induces the activation of microglia and the production of proinflammatory factors including nitric oxide (NO) and prostaglandins (PGs). We examined the effect of LPS on seizure susceptibility of mice, by using the sensitive test, threshold of clonic seizures induced by i.v. infusion of pentylenetetrazole. LPS decreased the seizure threshold in a dose- and time-dependent manner. Pretreatment of mice with the NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester or cyclooxygenase inhibitor, piroxicam or the opioid receptor antagonist, (-)-naloxone completely reversed the proconvulsant effect of LPS. These results indicate that NO, PGs and endogenous opioid peptides seem to be involved in LPS-induced decrease in seizure threshold.