In the present study, a large-scale retrospective case review was undertaken to assess the incidence and type of sexual dysfunctions associated with serotonin reuptake inhibitor (SRI) therapy, in addition to the effects of three pharmacological antidotes (yohimbine, amantadine, cyproheptadine) on SRI-induced sexual dysfunctions. A retrospective chart review was conducted on 596 patients treated with SRIs in an outpatient psychiatric practice between July 1991 and September 1994. Patients who reported new-onset sexual dysfunction during this time were categorized as having SRI-induced sexual dysfunctions. Sexual difficulties were characterized by type and duration, and the background characteristics and psychiatric diagnoses of all patients were recorded. Psychiatric outcome and sexual functioning at follow-up were independently assessed by a single psychiatrist by means of a 4-point rating scale. Sexual dysfunction symptoms were clearly associated with SRI administration in 97 (16.3%) cases. The most common problems reported were orgasmic delay or anorgasmia and hypoactive sexual desire. Sexual difficulties were more frequent among men (23.4%) and married patients of both sexes (22.3%), whereas psychiatric diagnosis and type of SRI were unrelated to the occurrence of sexual problems. Of the patients with sexual dysfunction, 45 (46.4%) opted for a trial of antidote therapy with yohimbine, amantadine, or cyproheptadine. All three antidotes were found to be safe and relatively effective, although yohimbine was significantly more effective than amantadine or cyproheptadine in reversing SRI-induced sexual dysfunction.