Recognition of social anxiety disorder (social phobia) as a common and disabling condition has led to new advances in its pharmacotherapy. Limitations with selective seroton reuptake inhibitors (side effects) and behavior therapy (scarcity of trained therapists), coupled with the tendency for patients with the disorder to self-medicate with alternative treatments, have led to the interest in Saint John's wort (SJW) (Hypericum perforatum) for this disorder. Although the literature is mixed, SJW has demonstrated efficacy in several double-blind depression trials, and some open-label studies with anxiety disorders. There is pharmacokinetic evidence for the serotonergic, domaminergic, and GABAminergic activity of hypericum, all of which are implicated in social anxiety disorder. This study was designed to generate pilot data to examine the potential efficacy of SJW in generalized social anxiety disorder. Forty subjects were randomized to 12 weeks of treatment with a flexible dose (600-1800 mg) of SJW (n = 20) or placebo (n = 20). Subjects with comorbid depression (clinician HAMD > 16) were excluded. Results found no significant difference between mean change on the Liebowitz Social Anxiety Scale with SJW (11.4) and placebo (13.2), P = 0.27, effect size = -0.09. Post-hoc analyses found larger effects sizes associated with increased baseline severity, omitting patients with variable scores (+/-30%) during the first week, and use of self-report HAMD scores for exclusion. Results of the study fail to provide evidence for the efficacy of SJW in social phobia. The impact of methodologic improvements on signal detection, while suggestive of improvement, remains to be established.