The spontaneous activity of rats was measured after activation or inhibition of GABA activity in the ventral tegmental area of the midbrain (VTA). Six hours after bilateral injection of ethanolamine-o-sulphate (GABA agonist) into the VTA, the behavioural activation induced either by d-amphetamine (amph) or by bilateral VTA infusion of a long-lasting enkephalin analogue was completely blocked. Bilateral infusion of picrotoxin (GABA antagonist) into the VTA elicited a short-lived (40 min) dose-dependent behavioural activation which was not reduced either by prior specific lesion of the meso-cortico-limbic dopaminergic neurones or by administration of the opiate antagonist naloxone. Moreover, the simultaneous administration of picrotoxin and amph induced complex changes in behaviour which consisted of additive effects during the first 40 min, followed by an inhibition of the activating effect of amph. Our findings indicate that GABA-mediated inhibition involves both dopaminergic and non-dopaminergic neurones within the VTA, and possible implications for human pathology are discussed.