Two receptors with high affinity for salmon calcitonin were cloned from the nucleus accumbens region of rat brain. The deduced 479 amino acid sequence of cDNA clone L2175-D20 (designated C1a receptor) is 78% and 66% identical with those reported for human and porcine calcitonin receptors, respectively. Clone U3237-A2 codes for a receptor (designated C1b) that is identical to C1a except for a 37 amino acid insert in the second extracellular domain. COS-7 cells transfected with either transcript bound [125I]salmon calcitonin with high affinity (Kd = 8 pM for C1a; Kd = 48 pM for C1b) and responded to salmon calcitonin with increases in cAMP. Tissue distribution studies revealed C1a transcript in rat brain, skeletal muscle, kidney and lung, whereas C1b was predominantly found in brain.