Our previous work4has demonstrated that medications known to increase the risk of IPAH (ie, fenfluramine, d-fenfluramine, and aminorex) share the common ability to serve as potent substrates for SERT proteins. Stimulants that are not associated with IPAH, such as amphetamine and phentermine,5 are weak substrates for SERT.6 Chin et al1 correctly pointed out that our in vitro findings showed that d-amphetamine and METH are much more potent dopamine and norepinephrine transporter substrates when compared to their activities as SERTs. For example, the concentrations of d-amphetamine and METH as dopamine transporters having 50% of the effect compared to the control are approximately 25 nmol/L, whereas their corresponding values as SERTs are 1,765 and 736 nmol/L, respectively. Such data predict that pharmacologic doses of these drugs should not release 5-hydoxytryptamine (HT) in vivo. Consistent with this prediction, doses of d-amphetamine that elevate extracellular dopamine levels in the rat brain do not elevate extracellular 5-HT levels in nervous system tissue,7and do not increase 5-HT levels in plasma.8 In marked contrast, METH administration produces similar elevations in extracellular dopamine and 5-HT levels in the rat brain, and also increases plasma 5-HT levels.7–8 Our data indicate that, in the case of METH, the profile of transporter activity determined in vitro does not predict the profile of activity in vivo.