To better understand the regulation of interleukin-9 (IL-9) receptor expression, we have isolated the genomic clone of the human IL-9 receptor based on its sequence homology with a human IL-9 receptor cDNA isolated from the human megakaryocyte cell line UT-7. The entire genomic structure has been determined. The human IL-9 receptor gene consists of 10 exons spread over approximately 13.7 kb of DNA. The nucleotide sequence of the coding region from the genomic DNA is identical to our cDNA clone. Several blocks of transcriptional control sequence have been identified at the 5' noncoding region of the IL-9 receptor gene that may play an important role in the regulation of the IL-9 receptor gene. A fusion gene containing 659 bp of human IL-9 receptor 5' noncoding region linked to the firefly luciferase gene directed expression of luciferase activity in human embryonic kidney 293 cell line, but not in the mouse fibroblast cell line NIH3T3 cells.