The study objective was to determine if serotonergic challenge with oral racemic fenfluramine would differentiate between childhood anxiety disorders in comparison to normal controls. Subjects were 24 children with anxiety diagnoses (DSM-IIIR) by structured interview, and 14 normal controls (ages 7 - 14 years) matched for age and sex. All subjects were given a standard challenge dose of d,1-fenfluramine (1 mg/kg) followed by serial assessments of cardiovascular, neurohormonal, and mood parameters over a five hour period. In response to fenfluramine, controls demonstrated increases in subjective anxiety and systolic blood pressure relative to anxious subjects. Fenfluramine was safely tolerated and did not induce panic symptoms in any subject. Exaggerated prolactin response to fenfluramine differentiated an obsessive - compulsive disorder (OCD) subset from both controls and other anxiety disorders. Fenfluramine challenge differentiates anxious children from healthy controls by elevated anxiety ratings and systolic blood pressure in controls. Increased prolactin response to fenfluramine discriminates children with obsessive - compulsive disorder from both healthy children and children with other anxiety diagnoses. As adults with OCD appear to demonstrate a blunted prolactin response to fenfluramine challenge, the serotonin pathways involved may differ between 'early' and 'late' onset disorder, or the serotonin substrates tapped by this challenge may change over time. Copyright 2000 John Wiley & Sons, Ltd.