The binding of [3H](R)alpha-methylhistamine to histamine H3-receptors in visual structures of unilaterally enucleated rats was examined by quantitative autoradiography to clarify the involvement of histamine neurons in the visual system. [3H](R)alpha-Methylhistamine binding in the visually deprived superior colliculus, contralateral to the enucleated eye, was significantly increased 5, 15, 30 and 45 days after unilateral enucleation. Slight time-dependent increases in ligand binding were observed in the visual cortex, but the change was significant only 45 days after unilateral enucleation. Unilateral enucleation had no significant effect in the dorsal lateral geniculate nucleus at any time after enucleation. Continuous injection of (S)-alpha-fluoromethylhistidine, a specific inhibitor of L-histidine decarboxylase, attenuated the effect of unilateral enucleation in the superior colliculus. These results suggest that retinal deafferentation induced an increase in histamine H3-receptor binding sites, probably by selective adjustment of histamine neurons in response to unilateral enucleation.