In this study the distribution of the calcitonin receptor isoforms, C1a and C1b, were mapped in rat brain using in vitro autoradiography and manipulation of their different pharmacological specificities. While salmon calcitonin binds to both receptors with high affinity, only the C1a receptor interacts with human calcitonin. Thus, the distribution of C1a specific binding sites was mapped using [125I]human calcitonin. The C1b receptors were mapped using [125I]salmon calcitonin in the presence of unlabelled human calcitonin and rat amylin, displacing binding of [125I]salmon calcitonin to C1a and C3 (amylin) sites, respectively. The distribution of C1a and C1b receptors was found to predominantly overlap. Brain regions displaying C1a, but little or no C1b, binding sites included the nucleus of the solitary tract, area postrema and the intermediate lobe of the pituitary. Although there were no nuclei expressing exclusively C1b receptors, parts of the mesencephalic and pontine reticular formation, and the thalamic paraventricular nucleus were enriched in C1b receptors relative to the density of C1a receptors in other brain regions. These data indicate that the relative expression of the two receptor isoforms, although predominately parallel, is not uniform in the rat brain.