Since 1976, benfluorex has been approved in Europe as a hypolipidemic and hypoglycemic drug, and is commonly used in the treatment of the metabolic syndrome. As a derivative of fenfluramine with an appetite suppressant action, benfluorex is preferentially used in overweight patients. In contrast to fenfluramine and dexfenfluramine, to date, benfluorex has not been reported to be associated with frequent cardiovascular side-effects. The present study reports five cases of severe pulmonary arterial hypertension and one case of valvular heart disease occurring in patients exposed to benfluorex. These individuals were middle age, diabetic females with a body mass index ranging 24.2-49 kg x m(-2). No definite causal effect for cardiovascular disease with benfluorex can be drawn from such case reports. However, as benfluorex, like dexfenfluramine and fenfluramine, is metabolised into active metabolite norfenfluramine, further extensive assessment of drug exposure in newly diagnosed pulmonary arterial hypertension or valvular heart disease patients is warranted.