Although St John's wort (Hypericum perforatum) is one of the most widely used and studied herbal medicines for depression, less is known about its efficacy in anxiety disorders, in spite of the fact that patients with anxiety disorders are among the most likely to self-medicate using alternative treatments. Pharmacokinetic evidence for the serotonergic, domaminergic and GABAminergic activity of hypericum, and a recent successful open-label study, suggests that it may be effective for obsessive-compulsive disorder (OCD). Sixty subjects were randomized to 12 weeks of treatment with St John's wort (LI 160) or matching placebo. Subjects with Hamilton Depression Scale scores of 16 or above were excluded. A flexible-dose schedule was utilized (600-1800 mg/day). The mean change on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) with St John's wort (3.43) was not significantly different than the mean change found with placebo (3.60) (P=899). No significant differences were found on any of the Y-BOCS subscales. The percentage of patients rated as 'much' or 'very much' improved at endpoint was not significantly different between St John's wort (17.9%) and placebo (16.7%) (P=0.905). Only one patient from each group discontinued due to adverse events [sinus infection (St John's wort); confusion (placebo)]. The results fail to support the efficacy of St John's wort for OCD.