1 A comparison has been made between the effects of microelectrophoretically applied naloxone on single neurones in the frontal cerebral cortex and the striatum of naive and of morphine-tolerant/dependent rats, anaesthetized with a mixture of alpha-chloralose and urethane. 2 Specificity of the results obtained was evaluated by contrasting the effects of alternate applications of the (+)- and (-)-isomers of naloxone to the same neurones. 3 In naive rats naloxone had predominantly no effect, only a few cells revealing non-specific depressant responses to the drug. 4 In morphine-tolerant/dependent rats a higher proportion of neurones responded to naloxone; either with stereospecific excitatory responses, in which the activity evoked by L-glutamate or acetylcholine was increased, or with a non-specific inhibition, similar to that observed in naive animals. 5 It is suggested that these excitatory responses to microelectrophoretically applied (-)-naloxone represent opiate withdrawal responses at the single neurone level and that they reflect a latent hyperexcitability of the postsynaptic membrane in the morphine-tolerant/dependent state.