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) oligodeoxynucleotide (oligo) against cloned μ or κ opioid receptors could block PL017- or dynorphin A-induced body temperature changes. Treatment with an AS oligo against μ receptors, but not sense (S) oligo, missence (MS) oligo or artificial cerebrospinal fluid (aCSF), abolished PL017-induced hyperthermia. In addition, treatment with an AS oligo against κ receptors, but not S oligo, MS oligo or aCSF, greatly attenuated dynorphin A-induced hypothermia. This study further supports the notion that μ and κ receptors mediate T b regulation.