When infused into the striatum of the rat, the excitotoxin quinolinic acid was found to eliminate neuropeptide Y (NPY)-immunoreactive nerve cell bodies and processes within the core of the injection area in a dose-dependent manner. This finding suggests that the NPY immunoreactivity in the striatum is entirely derived from a relatively small population of striatal NPY-producing interneurons. The striatal cholinergic neurons identified by means of the di-isopropylfluorophosphate (DFP)-pharmacohistochemical procedure for acetylcholinesterase were found to be more resistant than NPY-immunoreactive cells to the action of the neurotoxin. Similar results were also obtained following striatal injections of kainic acid. The fact that the striatal NPY-immunoreactive neurons are highly sensitive to quinolinic acid is not consistent with the recent proposal that this excitotoxin can be used as an experimental model of Huntington's disease where striatal NPY-positive neurons are selectively spared.