The effects of naloxone on acetylcholine (ACh) and gamma-aminobutyric acid (GABA) outflow from the cerebral cortex of freely moving, morphine-dependent guinea-pigs was studied. The cortical efflux of ACh in chronically-treated guinea-pigs was about half of that of normal animals. GABA efflux was unaffected. During opioid withdrawal precipitated by naloxone (0.1-10 mg kg-1, i.p.) the guinea-pigs showed jumping, hyperactivity and wet dog shakes, the intensity of which was directly related to the dose of naloxone. The withdrawal syndrome was accompanied by a dose-dependent increase in ACh release and reduction in GABA outflow; ACh release was increased by naloxone at doses lower (0.1-3 mg kg-1) than those acting on GABA efflux (1-10 mg kg-1). Atropine (10 mg kg-1) and diazepam (5 mg kg-1) did not prevent GABA and ACh changes.