A portion of the human calcitonin receptor (hCTR) gene corresponding to the region of the porcine gene at which alternative splicing generates two CTR isoforms was isolated by polymerase chain reaction amplification of placental DNA. In contrast to the porcine CTR gene, in which two acceptor sites in exon 8 are separated by 48 nucleotides, we found a distinct 48-nucleotide exon in the hCTR gene that is present approximately 6400 basepairs from the up-stream exon, which corresponds to porcine exon 7, and approximately 1100 basepairs from the down-stream exon, which corresponds to porcine exon 8. Splicing of this exon accounts for the two isoforms of hCTR, containing or not containing a 16-amino acid insertion in the first putative intracellular loop. A region similar to the intron 7-exon junction in the porcine CTR gene is present in the human gene, but contains four extra nucleotides that shift the reading frame. Using probes derived from these introns in somatic cell and in situ hybridization analyses, we assigned the CTR gene to human chromosome band 7q21.2-q21.3. Thus, human and porcine species have evolved distinct mechanisms to generate two similar CTR isoforms.