Locomotor activity was automatically recorded in a circular corridor in rats treated with 6-hydroxydopamine in the ventral tegmental area (VTA), septum and frontal cortex. Control and experimental groups showed similar hyperlocomotor responses in the novel apparatus lasting 3 h. Circadian changes are described. VTA lesions resulted in increased dark activity and a large response to apomorphine compared to other lesion and control groups. Septal lesions did not affect locomotion. The frontal group showed a small increase of locomotion after apomorphine treatment that might reflect increased receptor sensitivity in cortical or subcortical areas. Together with correlations between motor activity and cortical levels of dopamine and noradrenaline these results are interpreted to support a role for dopamine, noradrenaline and the frontal cortex in modulating locomotion which is primarily mediated by VTA-accumbens-dopamine activity.