The association between the tryptophan hydroxylase 1 (TPH1) 218A/C polymorphism and (1) severity of major depressive disorder (MDD) and (2) response to treatment was studied. There were three study populations, the first consisting of 119 treatment-resistant MDD inpatients treated with electro-convulsive therapy (ECT), and the second of 98 MDD open care patients treated with selective serotonin reuptake inhibitors (SSRI). In addition, there was a control population of 395 healthy blood donors. The first aim of the study was to compare the genotypes of the patient with those of the healthy controls and between patient populations. The second aim was to compare the genotypes of MDD patients achieving remission with basic SSRI treatment (MADRS<8) with the genotypes of non-responders to ECT (defined as MADRS>15). TPH1 218A/C polymorphism was associated with the risk of MDD. CC genotype was significantly more common in patients (including both ECT and SSRI treated patients) than in controls (38.2% and 26.8% respectively; p=0.008), and its frequency was significantly higher in more severe forms of depression, i.e. in ECT treated patients compared with SSRI treated patients (42.0% and 33.7%, p=0.026). CC genotype was also associated with lower probability of achieving remission. It was significantly more frequent among ECT non-responders than among SSRI remitters (53.1% and 23.3%, p=0.049). In this Finnish population TPH1 218A/C polymorphism was associated with the risk of MDD and treatment response; CC genotype was associated with the increased risk of MDD and lower probability of responding treatment. Further studies with larger samples will be required to confirm the results.