BACKGROUND A variety of drug treatments have been shown to be effective in the treatment of social phobia. This study attempted to assess the efficacy of nefazodone, a new novel serotonergic drug, in the treatment of social phobia. METHODS Nefazodone was administered to 23 patients who had a primary DSM-IV diagnosis of social phobia, generalized type (diagnosed by the Structured Clinical Interview for DSM-IV), in a 12-week open clinical trial. Treatment began at 100 mg of nefazodone daily and was increased according to clinical response and side effects. Patients completed self-report measures at baseline and at weeks 4, 8, and 12. These measures included the Fear of Negative Evaluation scale, the Social Avoidance and Distress scale, the Social Anxiety Thoughts Questionnaire, the Fear Questionnaire, the State-Trait Anxiety Inventory, the Beck Depression Inventory, the Social Adjustment Scale Self-Report, and the Sheehan Disability Scale. Clinicians completed the Liebowitz Panic and Social Phobic Disorders rating form and the Brief Social Phobia Scale. RESULTS Twenty-one of the 23 patients completed the 12-week trial. Sixteen (69.6%) were considered responders (moderate or marked improvement), and 7 (30.4%) were considered to be nonresponders (minimal improvement or no change in symptoms). Measures of social anxiety, social phobic avoidance, depression, and social functioning showed a statistically significant change at endpoint. CONCLUSIONS These findings support a role for nefazodone in the treatment of social phobia, generalized type. Controlled studies will be required to further investigate this preliminary finding as well as to compare nefazodone with other pharmacologic treatments of social phobia.