Patients receiving opioids report feeling sleepy, but opioids actually inhibit the rapid eye movement phase of sleep (REM). Inhibition of REM sleep is followed by a rebound increase in REM sleep associated with cardiopulmonary complications. The medial pontine reticular formation (mPRF) is a brain region from which morphine can inhibit REM sleep. The present study tested the hypothesis that specific subtypes of opioid receptors within the mPRF mediate inhibition of REM sleep. Synthetic opioid agonists selective for mu, delta and kappa subtypes were microinjected into the mPRF of four awake cats and polygraphic recordings of sleep and breathing were obtained. An enkephalinase inhibitor was microinjected into the mPRF to assess the contribution of endogenous opioids to the control of sleep and breathing. Only the mu agonist significantly inhibited REM sleep, and no opioid depressed breathing. These results demonstrate that opioid-induced REM sleep inhibition is mediated by mu receptor subtypes in the mPRF.