Serotonin (5-hydroxytryptamine) has been recently shown to be an important mediator of coronary vasospasm. Its divergent effect on normal and atherosclerosed arteries has been demonstrated in both animal and human studies. We present a case of coronary vasospasm in a 55-year-old man with repeated episodes of chest pain following coronary percutaneous intervention. Repeat angiography demonstrated no reocclusion or complication. The patient's symptoms were resistant to treatment with maximum doses of two calcium channel antagonists and oral and intravenous nitrates, but responded to cyproheptadine, a nonselective serotonin antagonist. Currently, there are only two reported cases of coronary vasospasm following balloon angioplasty responding to treatment with serotonin antagonists. This is the first case reported case following drug-eluting stent deployment.