The effects of local injections of drugs into terminal areas of the mesolimbic dopamine system were investigated. Bilateral administration of dopamine, but not of noradrenaline and serotonin, into the nucleus accumbens of non-pretreated rats resulted in stimulation of locomotor activity. No clear or only minor effects were seen after injections of the dopamine metabolites 3-methoxytyramine, DOPAC and HVA and after injections of media with different pH and osmolality. d-Amphetamine proved more effective than dopamine in producing locomotor stimulation, whereas both stimulant and depressant effects were observed following injection of apomorphine into the nucleus accumbens. ET 495 and the noradrenaline agonists clonidine, phenylephrine and isoprenaline did not enhance locomotor activity, but theophylline was effective. Pretreatment with haloperidol, but not with clozapine, significantly reduced the effects of dopamine and theophylline. Locomotor stimulation was also found following bilateral administration of dopamine, d-amphetamine and apomorphine into the tuberculum olfactorium, whereas noradrenaline, serotonin and ET 495 produced no, or rather depressant effects. These results provide further evidence for an important role of the mesolimbic dopamine system with respect to locomotor activity.