Alterations in the level of the serotonin, serotonin uptake and the number of binding sites have been linked to affective illness. We investigated the association of tryptophan hydroxylase gene polymorphisms and unipolar depression in a case-control study design.Patients and ethnically matched controls were genotyped for three polymorphisms of the tryptophan hydroxylase gene. RESULTS Significant difference in genotype frequency between patient and control groups was observed for the IVS7+218A >C polymorphism but not for the two promoter polymorphisms -1067G >A and -347T >G. Strong linkage disequilibrium among the three polymorphisms was also observed.As the sample size was small, the positive association would need to be replicated by family-based association studies or in a larger set of samples. As our results did not indicate association with either of the two promoter polymorphisms, there is a need to continue the search for the causative variant directly involved in the susceptibility to unipolar depression in Chinese as this polymorphism within the intron might not be the true susceptibility variant.