Background: Polymorphism in intron 7 of the tryptophan hydroxylase (TPH) gene was associated with bipolar affective disorder (BPD) in French. This study investigates whether the TPH gene is a susceptibility factor for the BPD in Taiwan by population-based association analysis. Methods: The TPH intron 7 A218C polymorphism was determined by using a polymerase chain reaction (PCR)-based method in 42 Taiwanese bipolar patients and 70 matched healthy controls. Results: A significant association of the TPH polymorphism to Taiwanese bipolar patients was obtained (P=0.03). In addition, a marginal association of CC genotype comparing to AC and AA genotypes with BPD was also observed (P=0.05). Conclusions: The present study confirms association between the tryptophan hydroxylase gene and bipolar disorder in Taiwanese thus suggesting a functional variant(s) in or close to the TPH gene may predispose individuals to bipolar disorder.