To delineate the involvement of spinal 5-HT1C receptors in supersensitivity and recovery following neonatal 5,7-DHT lesions, we injected rats on postnatal days 2 and 5 with 5,7-DHT or vehicle by intraperitoneal (IP) or intracisternal (IC) injection. [3H]Mesulergine-labelled sites measured 4 or 14 weeks later exhibited a significant increase (+35% for IP and 27% for IC) in Bmax without changes in Kd or nH. Spinal 5-HT content was significantly reduced (- 80 to 89%) by either route of 5,7-DHT injection. These data describe novel upregulation of spinal 5- HT1C receptors in rats with neonatal 5,7-DHT lesions. Spinal 5-HT1C receptor upregulation may contribute to the behavioral supersensitivity to L-5-hydroxytryptophan (L-5-HTP) in rats with 5,7-DHT lesions. It does not explain the behavioral recovery we found previously only after IP 5,7-DHT injection. © 1990.