A single oral dose of 15 mg/kg of fenfluramine reduced the level of serotonin in rat brain to 48, 51 and 63% of control at 1, 15 and 30 days, respectively, after administration. 3 mg/kg p.o. of the drug caused a smaller but significant diminution in brain serotonin. At the 3 mg/kg dose level, the decreases in serotonin were, at least partially, cumulative following multiple injections spaced 24 hr apart. Brains removed 14 days after the 5th daily injection of 5 mg/kg p.o. of fenfluramine had only 60% of the concentration of serotonin found in brains from control animals. These findings demonstrate that fenfluramine has a long-lasting action on serotonin-containing neurons in brain.