A new family of signal transducing proteins, associated with members of the tumour necrosis factor receptor (TNFR) superfamily, has recently been identified. The structural hallmark of these molecules is a novel C-terminal homology region of 230 bp designated as TRAF (TNF receptor-associated factor) domain, which is involved in a variety of specific protein-protein interactions. To elucidate the human TRAF1 gene structure for identification of potential regulatory elements, a set of genomic polymerase chain reaction (PCR) fragments was generated, which comprised the whole coding region of TRAF1. These fragments were cloned and partially sequenced to map splicing sites. The human TRAF1 gene was found to have a total length of approx. 12 kb. It is split into six exons, four of which encode for parts of the TRAF domain. Analysis of the genomic structure of the TRAF domains of human TRAF2 and 3 suggests that these domains are also encoded by several exons. The putative promotor region of the TRAFI gene was isolated by use of a PCR-based genomic walking approach. Fluorescence in situ hybridization was used to map this gene to chromosome 9q33-34.