We examined allelic polymorphisms of the serotonin transporter (5-HTT) gene and antidepressant response to 6 weeks' treatment with the selective serotonin reuptake inhibitor (SSRI) drugs fluoxetine or paroxetine. We genotyped 120 patients and 252 normal controls, using polymerase chain reaction of genomic DNA with primers flanking the second intron and promoter regions of the 5-HTT gene. Diagnosis of depression was not associated with 5-HTT polymorphisms. Patients homozygous I/I in intron2 or homozygous s/s in the promoter region showed better responses than all others (p < 0.0001, p = 0.0074, respectively). Lack of the I/I allele form in intron 2 most powerfully predicted non-response (83.3%). Response to SSRI drugs is related to allelic variation in the 5-HTT gene in depressed Korean patients.