The possibility that the GABAA receptor is involved in supraspinal morphine analgesia was investigated in rats using pentobarbital and other GABAA receptor-chloride channel ligands. Inhibition of tail-flick was used as an index of analgesia. Pentobarbital almost completely reversed intracerebroventricular (i.c.v.) morphine analgesia, but did not affect intrathecal (i.t.) morphine analgesia. Phenobarbital had a similar effect but was much weaker. Picrotoxin blocked the reversal effect of pentobarbital. Diazepam, when given together with pentobarbital, enhanced the effect of pentobarbital. Furthermore, muscimol reversed i.c.v. morphine analgesia without affecting i.t. morphine analgesia. Our results strongly suggest that the GABAA receptor is involved in supraspinal morphine analgesia.