The single-copy gene coding for the human parathyroid hormone-like peptide was isolated from a human placental genomic library. The gene spans 13 kilobases and contains seven exons. Exons I and II encode 5''-noncoding regions; each has its own transcription initiation site, and the two promoters are separated by over 1000 base pairs of genomic DNA. Exon III encodes the prepro-coding region, and exon IV encodes the mature peptide sequence. At the end of exon IV the splice site interrupts codon 139 of the mature peptide. Exon V, which is contiguous with exon IV, encodes a stop codon and a 3''-noncoding region. Exon VI encodes 34 additional amino acids, a stop codon, and a second 3''-noncoding region. Exon VII encodes two extra amino acids, a stop codon, and a third 3''-noncoding region. This genomic organization reveals how the multiple human parathyroid hormone-like peptide RNA transcripts, which have been observed, arise by both alternative splicing out of exons and use of multple promoters. The mRNAs, which can potentially be formed from the primary transcripts of this gene, could have one of three different carboxyl-terminal coding regions. The use of different exons to encode the different functional domains, 5''-noncoding regions, pre-pro-coding region, and mature peptide regions is identical to the organization of the human parathyroid hormone gene. This strongly suggests a common evolutionary origin of the two genes.