Serotonergic dysfunction is implicated in mood disorders and suicidal behaviors. Genetic variants of tryptophan hydroxylase (TPH), a rate-limiting enzyme in the biosynthesis of serotonin, were associated with suicidal behaviors in three reports, but were not found in other studies. We investigated the TPH A218C polymorphism in 151 subjects with mood disorders and 200 control subjects. The results demonstrated a significant difference in genotypic distribution between controls and depressed patients, but not bipolar patients. A positive association between TPH polymorphism and suicidal behaviors was found in depressed patients and not in bipolar patients. We suggest that the association of TPH variants and suicide might depend on the diagnosis, and TPH mutation plays no major role in the pathogenesis of bipolar disorders.