The effect of fenfluramine, an anorectical drug, given for nine months to a group of 156 obese subjects, on body-weight and adipose mass reduction as well as on glucose tolerance, has been studied. Subjects were divided in four different groups according to various protocols of therapy: the first group took the drug once a day in a single 60 mg dose in the morning; the second group received the drug once a day in a single 40 mg dose in the morning; the third group took the drug divided in three equal daily doses and the last group was treated with diet alone. During the first three months of treatment, fenfluramine 60 mg, given both in a single dose in the morning and divided in three equal daily doses, combined with diet, produces a significant body-weight reduction in comparison with the group of obese subjects treated with diet alone. In the following three months, it was possible to document a further body weight loss in all subjects, whatever the group to which they were assigned. At the end of the sixth month of observation, only slight differences could be demonstrated among the groups as regards the body-weight and adipose mass decrease. In addition the results failed to demonstrate a statistically different weight loss when the drug as administered in a single dose in the morning, compared with the conventional treatment of three times a day. No significant improvement of glucose tolerance was documented. In conclusion, in long-term treatment with fenfluramine, in contrast with short-term studies, no direct effect of this drug on body-weight and adipose mass decrease was demonstrated.