The cholecystokinin gene (CCK) is thought to play a role in the pathogenesis of both panic disorder and schizophrenia. In this study, we have extended the 5'-upstream sequence of the CCK gene, and identified a compound short tandem repeat (STR), located approximately -2.2 to -1.8 kb from the cap site. This STR was found to be polymorphic with ten different allele lengths. Case-control studies using 73 panic patients, 305 schizophrenics and 252 controls showed a significant allelic association with panic disorder (P = 0.025), but not with schizophrenia. Dividing the STR alleles into three classes according to length, Long (L), Medium (M) and Short (S), produced strong genotypic (MM) (nominal P = 0.0014) and allelic (M) (nominal P = 0.0079) associations with panic disorder. screening the newly extended promoter region detected not only the previously identified -36c>t and -188a>g single nucleotide polymorphisms (SNPs) but a new rare snp, -345g>C. Neither of the former two SNPs showed significant association with either panic disorder or schizophrenia. Haplotypic distributions of the STR and SNPs -188 and -36 were significantly different between panic samples and controls (P = 0.0003). These findings suggest that the novel STR or a nearby variant may confer susceptibility to the development of panic disorder.