Chronic administration of iminodipropionitrile (IDPN) to rats causes a persistent behavioral syndrome consisting of lateral and vertical twitches, random circling, hyperactivity, and increased startle response. These abnormalities are almost identical to those seen after acute injection of serotonin agonists and hallucinogenic drugs. The results of our quantitative autoradiographic localization studies comparing the distribution of 125I-lysergic acid diethylamide (LSD)-labeled 5-HT-2 serotonin receptors in slide-mounted sections of IDPN- and saline-treated revealed a number of changes in 5-HT-2 receptors in the brain of IDPN-treated animals. There were significant increases in the density of 5-HT-2 receptors in the frontal cortex, the cingulate cortex, and the claustrum in IDPN-treated rats. In contrast, there were significant decreases in the density of 125I-LSD binding sites in the nucleus accumbens and in the ventral region of the striatum. The present data provide further evidence to support the notion that the serotonergic system is involved in the manifestation of the persistent abnormalities induced by IDPN.