PL017 and dynorphin A(1-17) were shown previously to cause a marked increase and a profound decrease in body temperature (T-b), respectively. In this study, we examined whether an antisense (AS) oligodeoxynuoleotide (oligo) against cloned mu or kappa opioid receptors could block PL017- or dynorphin A-induced body temperature changes. Treatment with an AS oligo against mu receptors, but not sense (S) oligo, missense (MS) oligo or artificial cerebrospinal fluid (aCSF), abolished PL017-induced hyperthermia. In addition, treatment with an AS oligo against kappa receptors, but not S oligo, MS oligo or aCSF, greatly attenuated dynorphin A-induced hypothermia. This study further supports the notion that mu and kappa receptors mediate T-b regulation.