42 obese women who lost at least 6 kg after 26 weeks on fenfluramine tablets had their treatment changed to either an equivalent dose of a sustained-release preparation of fenfluramine or matching placebo in double-blind fashion. Of the 21 given placebo all but 2 regained weight over the following year. Of the 21 crossed over to fenfluramine, 8 maintained their weight loss, 7 regained weight, and 6 had to be withdrawn for reasons other than weight gain. Plasma concentrations of fenfluramine and norfenfluramine taken before and 4 weeks after the crossover were similar in both responders and non-responders, but non-responders did not maintain their drug levels for as long as did the responders. Longer controlled administration of fenfluramine will prevent weight regain in some obese women but the hazards of prolonged use remain to be evaluated.