Toluene inhalation (0.7% in air) induced in rats abnormal neurological states resembling the serotonin syndrome, such as hindlimb abduction, resting tremor and head weaving. The frequency and intensity of these responses were unchanged after two weeks of exposure (0.7% in air, 15 min/day for 14 days), indicating an absence of tolerance development. An examination of specific serotonin (3H-5HT) binding to crude synaptic membranes prepared from brains of rats subjected to acute and chronic toluene exposure revealed that while no changes in either apparent Kd or apparent Bmax occurred in acutely exposed animals, in chronically treated animals specific (3H)-5HT binding decreased in hippocampus and pons + medulla oblongata. These results indicate that serotonergic mechanisms may play a role in some of the effects of toluene inhalation in rats, but cannot explain the absence of tolerance development after chronic exposure to toluene.