Taijin kyofusho (TKS) has been categorized as a "culture-bound" illness that is unique to the East, although an alternative view holds that some TKS patients are best conceptualized as having a form of social anxiety disorder (SAD). However, pharmacotherapeutic interventions for TKS have not yet been rigorously investigated. A review was undertaken of 48 TKS patients initially treated with serotonin reuptake inhibitors (SRIs) in an outpatient setting of a Japanese hospital. Psychiatric diagnoses were determined according to DSM-IV, and a set of TKS diagnostic criteria based on a modification of DSM-IV SAD criteria. In addition, response to SRIs (clomipramine and fluvoxamine) was evaluated retrospectively using the Clinical Global Impressions (CGI) scale. All 48 patients met SAD-based TKS diagnostic criteria. In the pretreatment assessment, DSM-IV Axis I diagnoses included SAD (38%), major depressive episode (27%), and delusional disorder somatic type (15%). Sixteen (48%) of 33 patients treated with clomipramine or fluvoxamine for at least 6 months were categorized as responders (CGI = 1 or 2). Compared to responders, non-responders were significantly less likely to have pretreatment major depression, and significantly more likely to have comorbid cluster A personality disorders and to have received augmentation with antipsychotic drugs. Although TKS may be a heterogeneous condition with various comorbidities, patients invariably fulfilled diagnostic criteria for TKS based on SAD criteria. SRIs may be effective for a substantial number of TKS patients. Prospective controlled trials are necessary to confirm these findings and to delineate the pharmacotherapeutic profile of TKS.