Intraventricular injections of 6-hydroxydopamine in 3-day-old rats resulted in the near-total loss of tyrosine-hydroxylase-immunoreactive processes in the striatum when examined 2-6 months later. This destruction of dopamine (DA) afferents was accompanied by an increase in the density of serotonin (5-HT)-immunoreactive fibers in the striatum. The hyperinnervation was most striking in the rostral striatum, an area containing few 5-HT-immunoreactive fibers in control rats. Retrograde tracing, with either horse-radish peroxidase or rhodamine-labelled microspheres, indicated a significant increase in the number of neurons projecting to the rostral striatum from the dorsal raphe nucleus of lesioned animals. The increase was largely confined to the rostral extent of the dorsal raphe, and overlapped the distribution of cells labelled after injections of HRP into caudal striatum of control and lesioned animals. In sections additionally processed for immunocytochemistry, 80-90% of retrogradely labelled raphe neurons in both groups of animals were found to be 5-HT-immunoreactive. None of changes encountered in infant-lesioned rats were observed 2-4 weeks after 6-HDA was given to adult animals. These findings demonstrate that removal of DA afferents during development leads to an enlargement of the serotoninergic projection from the raphe nucleus to the striatum.