Exogenous substances such as the appetite suppressant fenfluramine are known to be causally related to the development of pulmonary arterial hypertension (PAH). In these cases, the clinical course as well as the pulmonary vascular disease pathologically is indistinguishable from idiopathic PAH. Other exogenous substances, such as amphetamines, cocaine, and meta-amphetamines, have been considered to be potential risk factors for inducing PAH. SOPHIA (the study of pulmonary hypertension in America), in addition to confirming previous reports of a causal association between the appetite suppressant fenfluramine and PAH, unexpectedly found a significantly increased risk for the development of PAH with exposure to over-the-counter antiobesity agents containing phenylpropanolamine. The first case is reported of fatal PAH in a child heavily treated with cold remedies containing phenylpropanolamine, which, in addition to the results of SOPHIA, strengthens the hypothesis that phenylpropanolamine is a risk factor for the development of PAH.