Inter-alpha-trypsin inhibitor family heavy chain-related protein (IHRP) is a novel glycoprotein isolated from human plasma. The cDNA encoding IHRP has recently been cloned from human liver cDNA libraries. We report the mapping of this gene (ITIHL1) by fluorescence in situ hybridization using a 2.5-kb cDNA fragment as a probe. ITIHL1 was localized to chromosome region 3p21-->p14 where the genes of heavy chain 1 and 3 of inter-alpha-trypsin inhibitor are located. This result, together with significant homology between the nucleotide sequences of ITIHL1 and the heavy chain genes, supports ITIHL1 as being a member of an evolutionary related gene family of ITI heavy chains. Northern blot analysis indicated that IHRP was predominantly synthesized in liver. From Southern blot analysis, it was tentatively concluded that ITIHL1 is a single copy gene.