The aim of this study was to compare the functional effects of neonatal, weanling and adult lesions of the dopaminergic (DA) mesencephalic neurones on paw-reaching behaviour. The mesotelencephalic DA pathway was destroyed unilaterally in neonatal (3 and 7 day), weanling (21 day) and adult (2 months) rats by local injection of 6-hydroxydopamine into the medial forebrain bundle at the level of the lateral hypothalamus, followed by behavioural studies conducted 2 months later. Amphetamine and apomorphine induced similar rates of rotation irrespective of the age of the lesion. By contrast skilled reaching with the contralateral paw was profoundly disrupted by lesions made in adult or weanling rats, but a much reduced deficit was observed in neonatally lesioned rats. Tyrosine hydroxylase immunohistochemistry indicated a similar degree of dopamine cell loss from the substantia nigra in all groups. These observations suggest that the host brain undergoes developmental changes 1-3 weeks postnatally that influence the long-term effects of lesions in the nigrostriatal dopamine system.