The aim of our study was to determine whether serotonergic hyperinnervation is rapidly induced in the striatum of adult rats with extensive dopaminergic denervation. Immunohistochemical study was performed on the brain sections obtained at 2 and 8 weeks after injection of 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. The extent of dopaminergic denervation was evaluated as a percentage loss of tyrosine hydroxylase immunopositive neurons in the substantia nigra pars compacta. The immunopositive areas for serotonin (5-HT) in the striatum were measured. In the lesioned rats 97.5+/-0.6% of dopamine neurons were lost. 5-HT immunopositive areas in the striatum were significantly increased both at 2 and 8 weeks after 6-OHDA injection (P<0.01). These results suggest that extensive dopaminergic denervation in adult rats induces rapid serotonergic hyperinnervation in the striatum as early as 2 weeks after lesioning.