The opiate antagonist naloxone has been reported to cause pain relief. Therefore, the effect was determined of naloxone, injected intravenously, on the activity in single neurones of the dorsomedial part of the ventral nucleus (VDM) in the thalamus of rats under urethane anaesthesia elicited by electrical stimulation of nociceptive afferents in the sural nerve. Naloxone inhibited evoked nociceptive activity in a dose-dependent manner. High doses (5 mg/kg and 1 mg/kg) either increased or reduced the activity, inhibition prevailing at the lower dose. At lower doses (0.5 mg/kg, 0.2 mg/kg and 0.1 mg/kg), naloxone caused only inhibition, the ED50 being 0.36 mg/kg. The (+)-isomer of naloxone (0.2 mg/kg and 2 mg/kg) was ineffective, indicating that the effects of naloxone, which is the (-)-isomer, are stereospecific. The opposing effects exerted by naloxone at high and low doses may be due to the processing of nociceptive messages delivered to the thalamus by multiple endogenous opioid systems with differing susceptibility to naloxone. The results present evidence that naloxone at low doses may cause relief in particular conditions of pain.