We have determined the exon/intron organization of the human phospholipid transfer protein gene. The gene, which spans approximately 13.3 kilobases, is comprised of 16 exons. The organization of the phospholipid transfer protein gene strikingly resembles that encoding another plasma lipid transfer protein, the human cholesterol ester transfer protein. The exon-intron junctions in these two genes are highly conserved, with eight out of fifteen junctions interrupting the same codons, while the remaining junctions lie within 5 residues of each other. The similarity in gene structure and homology in coding sequences suggests that these two genes most likely evolved from a common ancestral gene.