In this study, 16 overweight or obese NIDDM patients with a long period of stable weight and dietary surveillance were treated with 150 mg t.i.d. of Benfluorex per os for 3 months. A significant improvement occurred in the fasting and post-meal glucose levels and in the HbA1C values, regardless of weight changes that occurred throughout the study. No significant changes were found in the fasting or meal-stimulated insulin (IRI) levels and in the glucose:IRI molar ratios. On the contrary, there were no significant variations in C-peptide levels while the glucose:CPR ratio appeared to decrease while on Benfluorex. In basal conditions, 11 patients presented insulin insensitivity (as measured by the glucose-insulin-somatostatin technique) which was unaffected by the pharmacological treatment. Benfluorex may therefore ameliorate metabolic control in overweight or obese NIDDM patients, but our data do not clarify whether its effects are mediated by an improvement in the action of insulin in peripheral tissues.