Recent research suggests that central corticotropin releasing hormone hyperdrive is an important neurobiological risk factor for developing major depression. The availability of free corticotropin releasing hormone in the central nervous system is tightly regulated by the expression of corticotropin releasing hormone binding protein. Therefore, the gene encoding for corticotropin releasing hormone binding protein is a functional candidate gene for major depression.We present a systematic study of single nucleotide polymorphisms in the corticotropin releasing hormone binding protein gene and their role in the liability for major depression. Seven single nucleotide polymorphisms were genotyped in a well-diagnosed sample of 89 patients with recurrent major depressions and matched controls.Two single nucleotide polymorphisms within the corticotropin releasing hormone binding protein gene were significantly associated with the disease (p <.05). An expectation-maximization algorithm estimated a specific haplotype to have a frequency of 53% in patients and 35% in controls (p <.001).The corticotropin releasing hormone binding protein gene is likely to be involved in the genetic vulnerability for major depression.