Recently the clock genes have been reported to play some roles in neural transmitter systems, including the dopamine system, as well as to regulate circadian rhythms. Abnormalities in both of these mechanisms are thought to be involved in the pathophysiology of major mental illness such as schizophrenia and mood disorders including bipolar disorder (BP) and major depressive disorder (MDD). Recent genetic studies have reported that CLOCK, one of the clock genes, is associated with these psychiatric disorders. Therefore, we investigated the association between the six tagging SNPs in CLOCK and the risk of these psychiatric disorders in Japanese patients diagnosed with schizophrenia (733 patients), BP (149) and MDD (324), plus 795 Japanese controls. Only one association, with schizophrenia in females, was detected in the haplotype analysis (P = 0.0362). However, this significance did not remain after Bonferroni correction (P = 0.0724). No significant association was found with BP and MDD. In conclusion, we suggest that CLOCK may not play a major role in the pathophysiology of Japanese schizophrenia, BP and MDD patients. However, it will be important to replicate and confirm these findings in other independent studies using large samples.