The effects of nitrous oxide (N_2O : 75%) or pentobarbital (PB : 80mg/kg intraperitoneal) on substance P (SP) synaptic transmission in the central nervous system were examined in 23 rats. For evaluation of SP receptor function, specific binding of [^<125>I] -Bolton Hunter SP was determined, using in vitro quantitative autoradiography. The number od receptors (Bmax) and affinity constant (Ka) in the discrete 12 regions of the central nervous system were determined by equilibrium binding method following by Scatchard analysis. In the N_2O group, the Bmax significantly decreased by 22% in spinal cord (laminae I-II), but increased significantly by 41% in locus coelureus (LC) and by 31% in cental gray at the end of 2-hour N_2O exposure as compared to the awake control values. These changes became insignificant within 12 hours after the end of N_2O exposure. In the PB group, the Bmax significantly increased by 30% in LC, but decreased By 21-32% in hippocampus (HIP), amygdala (AMY), septal nucleus (SEP) or caudate-putamen (CP), the Ka significantly increased by 144, 133 and 109% in solitary nucleus, SEP and CP, respectively, at 2 hours after the administration of PB, as compared to awake control values. The Bma in HIP, AMY and SEP was remained decreased at 12hours after PB anesthesia. These results suggest that N_2O and PB differentially affect SP receptor functions in the specific regions of the cental nervous system.