CURRENTLY three subtypes of the 5-HT2 receptor have been identified through binding studies and/or molecular biology studies, 5-HT2A, 5-HT2B, and 5-HT2C. The identification of these receptor subtypes in the spinal cord of humans and experimental animal species is incomplete. In the present study, polymerase chain reaction with Southern hybridization analysis was used to determine whether the mRNA for the 5-HT2A, 5-HT2B and 5-HT2C receptors could be detected in spinal cord tissue from rats, cats, monkeys and humans. Brain tissue from rat, cat and monkey were also examined for comparison. 5-HT2A and 5-HT2B receptor mRNAs were amplified and localized with rat 5-HT2A and 5-HT2B primers and probes, respectively, in tissue from all species. In rats, 5-HT2C receptor mRNA was amplified and localized with rat 5-HT2C primer and mouse 5-HT2C probe, respectively, while in cat, monkey, and human tissue, human 5-HT2C primers and probes were used. Spinal cord from all four species contained mRNA for the 5-HT2A receptor. Brain tissue from rat, cat and monkey also contained 5-HT2A mRNA. Spinal cord tissue from ail four species contained 5-HT2B message. Brain tissue from cat and monkey contained 5-HT2B mRNA, but this was not detected in rat brain. 5-HT2C mRNA was detected in spinal cord and brain tissue from rat, monkey and human, but was only detected in brain tissue of the cat (i.e. no 5-HT2C mRNA was detected in cat spinal cord). In conclusion, mRNA for all three currently known 5-HT2 receptor subtypes was detected in spinal cord tissue of rat, monkey and human, while only 5-HT2A and 5-HT2B mRNAs were detected in cat spinal cord.