We present a 67-year-old right-handed male with a brachium pontis arteriovenous malformation on continuous anti-emetic therapy who demonstrated acute withdrawal symptoms after the abrupt discontinuation of ondansetron, a 5-HT(3) receptor antagonist. Removal of anti-emetic therapy led to the development of extreme flushing and tremor, but subsequent return of ondansetron resulted in the resolution of these symptoms. This is the first clinical report demonstrating acute withdrawal from an anti-emetic agent and we further highlight the need for future studies evaluating not only arterial supply with pressure gradients and anatomical location, but also the association with periventricular venous drainage, venous drainage stenosis, and mass effect from venous stasis as this may contribute partly to the sensitivity of the serotonergic receptors seen here.