Genomic clones containing a human coproporphyrinogen oxidase gene, were isolated. DNA sequencing indicates that the human CPX gene spans about 14 kb and consists of seven exons and six introns. Sequences were determined for all the exons, exon-intron junctions and for 800 bp of promoter region. Introns vary in size from 269 bp to 5 kb and they all have consensus sequences at their boundaries. Primer extension and ribonuclease protection experiments revealed multiple transcriptional initiation sites in a region with sequence motifs characteristic of a promoter. The promoter region is GC-rich and contains multiple potential Sp 1 elements, CACCC boxes and potential GATA-1 binding sites. The availability of the CPX genomic sequence allowed us to determine the mutation in a patient with a hereditary coproporphyria. AG to A mutation was found at the last position of exon 6. This mutation results in exon skipping.