To see if the opiate receptor/endorphin system plays a part in the regulation of natural sleep in humans the effects of the opiate antagonist naloxone on delta sleep were examined. The sleep behaviour of each of six healthy male volunteers aged 20-32 years was monitored by continuous recordings of EEG, EOG, EMG, heart rate and respiratory rate for 3 nights. The sleep stages were evaluated according to Rechtschaffen and Kales. Naloxone (0.03 mg/kg body wt.) or saline as placebo was administered intravenously in a double-blind randomized order during the spontaneously occurring delta sleep, the effects being observed on sleep behaviour and recorded variables. Naloxone never elicited arousal, either in the EEG or in the subjects' behaviour. The only effect noted was an increase in the mean latency of the first REM sleep stage. Naloxone does not arouse humans from natural delta sleep. It seems unlikely therefore, that endorphins play a role in the regulation of delta sleep in humans unless there are opiate receptor subtypes involved for which naloxone has a low affinity in man.