A transcription map was generated of a 1 Mb interval including the HFE gene on 6p22. Thirty-seven unique cDNA fragments were characterised following their retrieval from hybridisation of immobilised YACs to primary pools of cDNAs prepared from RNA of foetal brain, human liver, foetal human liver, placenta, and CaCo2 cell line. All cDNA fragments were positioned on the physical map on the basis of presence in aligned and overlapping YACs and cosmid clones of the region. The isolated cDNAs together with established or published sequence tagged sites (STSs) and markers provided sufficient landmark density to cover approximately 90% of the 1 Mb interval with cosmid clones. The precise localisation of two known genes (NPT1 and RING finger protein) was established. A minimum of 14 additional transcription units has also been integrated. Twenty-eight cDNA fragments showed no similarity with known sequences, but 20 of these detected discrete mRNAs upon northern analysis. Their characterisation is still under investigation. Eleven new polymorphisms were also identified and localised, and the HFE genomic structure was better defined. This integrated transcription map considerably extends a recently published map of the HFE region. It will be useful for the identification of genetic defects mapping to this region and for providing template resources for genomic sequencing.