OBJECTIVE: To report a case of a neurotoxic syndrome in a patient undergoing concomitant treatment with risperidone and fluvoxamine. CASE REPORT: A 24-year-old African American woman hospitalized for psychosis was unresponsive to risperidone. Because of obsessive symptoms, low doses of fluvoxamine were added to her treatment regimen. Within 2 days, she developed confusion, diaphoresis, diarrhea, hyperreflexia, and myoclonus, which then progressed to rigidity, fever, and unresponsiveness, requiring endotracheal intubation. Symptoms resolved over 10 days with discontinuation of medication, hydration, and bromocriptine 5 mg 3 × daily. Ultimately, she was treated with olanzapine and fluvoxamine without adverse effects. DISCUSSION: This represents the first reported case of a neurotoxic syndrome secondary to treatment with risperidone and fluvoxamine. Differential diagnosis between neuroleptic malignant syndrome (NMS) and serotonin syndrome (SS) could not be accurately determined because of the overlap of signs and symptoms of both syndromes. NMS and SS may represent different aspects of a more generalized neurotoxic syndrome. This could be an important consideration in formulating treatment for neurotoxic syndromes. CONCLUSIONS: Clinicians should be aware of potentially serious adverse reactions that may occur during concomitant treatment with antipsychotics and selective serotonin-reuptake inhibitors.