Matrix metalloproteinase-9 (MMP-9) plays a role in many pathological conditions (e.g., cancer and heart disease). Recently, MMP-9 has been implicated in various aspects of brain functions (e.g., neuroplasticity and epileptogenesis) and thus, we hypothesized that MMP-9 gene may be associated with bipolar mood disorder. The study was performed on 416 patients with bipolar mood disorder, including 75 patients with bipolar II type of the illness, and in 558 healthy control persons. A functional −1562C/T polymorphism of the MMP-9 gene was genotyped in all subjects. Patients with bipolar mood disorder had significant preponderance of T allele versus C allele of 1562C/T polymorphism of the MMP-9 gene, compared to healthy control subjects. The higher frequency of T allele compared to healthy subjects was especially evident in a subgroup of patients with bipolar disorder, type II. The results may provide the first evidence for an involvement of the MMP-9 gene in the pathogenesis of bipolar mood disorder. They may also contribute to explaining genetic connection between bipolar mood disorder and some somatic illnesses. In the light of our results obtained with this polymorphism in schizophrenia, we speculate that the MMP-9 gene may be a common susceptibility gene to major psychoses with different allelic variants occurring in bipolar illness and schizophrenia.