Receptor proteins for human calcitonin gene-related peptide (CGRP) have been demonstrated in the human cerebellum. Membrane homogenates were incubated with [125I] iodo CGRP-I and -II ([125I]CGRP). The bound radioligands were cross-linked to membrane proteins. Solubilized membrane proteins were separated by gel-electrophoresis. Autoradiography of the gels revealed specifically labeled ligand-protein complexes of Mr 17,500 and 54,000 for human CGRP-I and -II. Specific binding of [125I]CGRP-I and -II was only minimally affected by up to 0.5 microM salmon and human calcitonin. The affinity and specificity of CGRP-I and -II binding were the same in crude homogenates and in the purified binding proteins. In conclusion, indistinguishable binding proteins for [125I]CGRP-I and -II of 13,700 and 50,000 Da have been identified in the human cerebellum.