Normal function of the dopaminergic system is necessary for speech fluency. There was evidence that the activities of dopamine transporter (DAT) and dopamine D2 receptor (DRD2) could be altered in people with speech disfluency. This study aims to ascertain the possible correlation between two dopaminergic genes (SLC6A3 and DRD2) and disorder of speech fluency, and to determine the allelic frequencies of the five single-nucleotide polymorphisms (SNPs) (rs2617604, rs28364997, rs28364998 in SLC6A3 and rs6275, rs6277 in DRD2) among Han Chinese patients with this disorder. A sample of 112 patients with speech disfluency and 112 gender-matched controls were included in this case-control study. The results show that the presence of C allele at rs6277 in DRD2 gene is associated with increased susceptibility to the disorder, whereas T allele is protective. Haplotype 939T/957T is also a protective factor. Keywords: case-control study; dopamine D2 receptor; dopamine transporter; disorder of fluent speech; Han Chinese; SNPs INTRODUCTIONLanguage is a particular type of human cognitive function that can be divided into 'language' and 'speech.' 1 Speech production is a process that transforms conceptual ideas within the brain into specific language form and expresses it vocally. 2 Fluent speech depends on the balance of the three steps: conceptualization, formulation and articulation, 3 but the detailed mechanism has not been fully understood yet. Stuttering has been used as a model of speech disfluency to understand the mechanism of speech production. 4 It is characterized by involuntary syllable repetitions, syllable prolongations or interruptions (blocks) in a smooth flow of speech. Developmental stuttering begins during the period of rapid speech and language development in childhood and is characterized by a disturbance in the normal fluency and time patterning of speech. 5 Dopamine has a major role in fine motor movements, and speech requires the coordination of many small muscles. 6 The dopamine excess theory of stuttering suggests that stuttering may be related to excess levels of the neurotransmitter in the brain. [7][8][9] Further evidence for the theory came from attempts at treating stuttering with antipsychotic medications that block dopamine in the brain. 10-13 A study to evaluate the efficacy of risperidone in the treatment of developmental stuttering showed that a significant decrease of stuttering severity occurred in the risperidone treatment group than in that of the placebo group. 14 The risperidone research supports dopamine having a regulatory role in stuttering.