Here we investigated the effect of naloxone-precipitated morphine withdrawal on the release of noradrenaline in hippocampus of the anaesthetised rat. Naloxone (1 mg/kg i.p.) injected 3 and 24 h, but not 3 weeks, after eight daily injections of morphine, induced an immediate increase in hippocampal noradrenaline release. This striking effect of naloxone was markedly attenuated by pretreatment with clonidine (0.1 mg/kg s.c.). These findings provide direct evidence for a marked release of noradrenaline in hippocampus during opiate withdrawal in vivo.