The selective serotonin re-uptake inhibitors (SSRIs) are increasingly being used to treat depression and anxiety disorders. Gastrointestinal (GI) symptoms are the main side effects, probably resulting from the stimulation of central or peripheral 5-HT receptors. The present double-blind, placebo-controlled study was undertaken to see if the GI side effects of fluvoxamine could be attenuated by the co-administration of the 5-HT(3) antagonist ondansetron. The results demonstrate that, in volunteers, a single 100 mg oral dose of fluvoxamine can produce GI symptoms. Co-administration of ondansetron significantly reduced peak nausea and GI side effects, compared with placebo.