THE periaqueductal gray (PAG) and rostral ventrome-dial medulla (RVM) are important brain stem pain modulating regions. Recent evidence suggests that κ opioids antagonize the effects of μ opioids in the RVM. However, the anatomical relationship between μ and κ opioid receptors in PAG and RVM is not well characterized. This study examined relationships between μ and κ opioid receptor immunoreactivity (IR) and mRNA in PAG and RVM. Brain slices were processed for either immunocytochemistry orin situhybridization. We found considerable anatomical overlap of μ and κ opioid IR and mRNA in the RVM and PAG. These results provide an anatomical basis for recent behavioral and electrophysiological findings in RVM, and suggest modulatory interactions between μ and κ opioids in PAG.