We have determined the nucleotide sequence of the proximal 3625 nucleotides 5' flanking the major mRNA start site of the human corticotropin releasing hormone gene (hCRH) and identified several putative regulatory elements. Interestingly, we did not detect any glucocorticoid responsive elements; we did however find five interspersed perfect half palindromic estrogen responsive elements, which might confer estrogen regulatability to the hCRH gene. We have identified a segment spanning from -2835 to -2972, which has about 72% homology to the 3' terminal half of the human Alu I family of highly repetitive elements, and another one, which spans from -2213 to -2580 and has greater than 80% homology to members of human type O family of repetitive elements. These elements may confer DNA fragility, since the loci for hCRH and the human fragile site FRA8F colocalize in human chromosome 8. The structural information reported represents a first step in the study of regulation of the hCRH gene at the molecular level.