Secretin is the most potent regulator of pancreatic bicarbonate, electrolyte and volume secretion. In this report, the organization of the human secretin receptor (hSR) gene was characterized by overlapping genomic phage clones. The hSR gene consists of 13 exons and 12 introns with all the splice donor and acceptor sites conforming to the canonical GT/AG rule. By transient reporter gene assays, the wild-type promoter, containing 3.0 kb of the hSR gene 5P P flanking region, was able to drive 5.8 þ 0.6 and 6.6 þ 0.2-fold (P 6 0.01) increases in luciferase activities in pancreatic ductule-derived PANC-1 and BPD-1 cells, respectively. By subsequent 5P P and 3P P deletion analysis, a promoter element was identified within 3 3408 to 3 3158, relative to the ATG codon. This promoter element was found to be cellspecific since it could drive reporter gene expression in PANC-1 and BPD-1 cells but not in Hs 262.St, Hs 746T and K KT3-1 cells. The study of the transcriptional control of human secretin and its receptor should shed light on the pathological developments of pancreatic cancer and autism in the future.z 1999 Federation of European Biochemical Societies.