The distribution of specific calcitonin gene-related peptide (CGRP) binding sites was investigated in gerbil brain regions such as cortex, cerebellum, hypothalamus, and hippocampus. The binding of [125I]CGRP to membranes prepared from these regions of the gerbil brain was rapid, saturable and specific with dissociation constants (Kd) between 10-40 pM and maximum binding (Bmax) between 10-30 fmol/mg protein. Human and rat CGRP and hCGRP8-37 competed for [125I]hCGRP binding in a concentration-dependent manner with a Ki of 10-100 pM. Salmon calcitonin was very weak in competing for [125I]hCGRP binding (ki > 10 microM). CGRP did not stimulate adenylate cyclase in these brain regions. Cross-linking of [125I] hCGRP to the brain membrane fractions with disuccinimidyl suberate revealed specific incorporation of [125I] hCGRP to a protein band of approximate molecular weight 52 kDa.