We have injected lipopolysaccharide (LPS) into the nigrostriatal pathway of rats in order to address the role of inflammation in Parkinson's disease (PD). LPS induced a strong macrophage/microglial reaction in Substantia nigra (SN), with a characteristic clustering of macrophage cells around blood-vessels. The SN was far more sensitive than the striatum to the inflammatory stimulus. Moreover, only the dopaminergic neurons of the SN were affected, with no detectable damage to either the GABAergic or the serotoninergic neurons. The damage to the DA neurons in the SN was permanent, as observed 1 year postinjection. Unlike the direct death of dopaminergic neurons caused by agents as MPP(+) or 6-OHDA, LPS seems to cause indirect death due to inflammatory reaction. Therefore, we suggest that the injection of a single dose of LPS within the SN is an interesting model for studying the selective effects of inflammatory reaction on dopaminergic system and also potentially useful for studying PD.