The bindings of [3H](R) alpha-methylhistamine to histamine H3 receptors were investigated in rat brain following intranigral treatment with 6-hydroxydopamine (6-OHDA) by quantitative receptor autoradiography. The levels of [3H](R) alpha-methylhistamine binding sites in the denervated striatum (dorsomedial and dorsolateral) and substantia nigra were significantly higher than those in the contralateral side 21 days after nigral lesions. Saturation kinetic analysis revealed that the maximum binding capacities were up-regulated to about 1.7- and 1.2-fold those in the contralateral substantia nigra and striatum, respectively. These results strongly suggest that H3 receptors in the striatum and substantia nigra are influenced by tonic dopaminergic inputs.