Chronic fenfluramine administration prevented excess weight gain following ovariectomy in rats but did not alter weight gain in sham-operated controls. Chronic quipazine treatment had no long-term effect on body weight. In one experiment, fenfluramine treatment for 28 days produced a 13% decrease in [3H]-serotonin binding to hypothalamic membranes and no change in [3H]-spiroperidol binding to striatum. In a second experiment, however, chronic fenfluramine had no effect on [3H]-serotonin binding to diencephalon. These results are discussed in terms of central and peripheral mechanisms of action and tolerance to fenfluramine.