We report the characterization by genomics-based approach of the human H-4-receptor gene structure. The H-4-receptor gene have been mapped by radiation hybrid experiments (Gene Bridge 4) on chromosome 18q11.2, between the AFMBB11WH5 and CHLC.GATA85D10 markers. The H-4-receptor gene spans more than 21 kbp and contains three exons separated by two large introns (>7 kbp). RT-PCR analysis showed that the H-2-receptor gene encoded a 3.7 kb mRNA which did not seem to be alternatively spliced within its coding region. The H,receptor transcripts were found to be highly expressed in peripheral tissues implicated in inflammatory responses such as leukocytes, spleen, lung, and liver, In addition, low expression level of the H-4-receptor mRNA was also detected in several human brain regions. Analysis of the 5 ' -flanking region of the H-4-receptor gene did not reveal the existence of canonical TATA or CAAT-box. However, several putative regulatory elements mediating TNF alpha or IL-6-stimulated transcriptional activation were detected. The uteroglobin promoter binding factor, known to mediate anti-inflammatory response of uteroglobin, in the lung, was also found in this region. Thus, the description of the H, receptor gene promoter region will facilitate the elucidation of its transcriptional control by factors secreted during inflammatory responses.