P(1)450 and P(3)450 are the two members of the dioxin-inducible P450 gene family, one of at least eight families in the entire P450 gene superfamily. The human P(1)450 gene has been previously sequenced. In this report the human liver P(3)450 protein is shown to migrate as a 54-kDa band on NaDodSO4-polyacrylamide gel electrophoresis. The human P(3)450 cDNA (3,064 bp) and complete P(3)450 protein (515 residues; Mr = 58,294) were determined. The human P(3)450 mRNA (3.3 kb) has an unusually long 3' nontranslated region (1,509 bp) primarily due to the inclusion of four copies of Alu repetitive sequences. Comparison of human P(3)450 cDNA with human P(1)450 cDNA and mouse (or rat) P(3)450 cDNA with mouse (or rat) P(1)450 cDNA suggests that an intra-exonic gene conversion event (in the region between 100 and 400 nucleotides from the 5' end of the translated region) most likely occurred between 20 and 80 million years ago. Analysis of 32 human X mouse and 23 human X hamster somatic cell hybrids confirm unequivocally that both P(3)450 and P(1)450 reside on human chromosome 15.