To the Editor: The calcineurin pathway has been proposed to mediate left ventricular hypertrophy, particularly its initiation. 1 However, evidence has been scant. Braun et al 2 designed a very interesting experimental protocol and investigated whether calcineurin expression was up-regulated at the initial stage of left ventricular hypertrophy. Unfortunately, they failed to detect calcineurin overexpression. There are a couple of problems with the methodology they employed in the study. First, it appears that they homogenized the whole heart instead of the left ventricle only, which may dilute calcineurin expression. Second, calcineurin upregulation represents both increased calcineurin expression and increased calcineurin activity. Apparently, the activity was not measured in the study, as the assay for calcineurin has not been perfected. 3,4 As such, it remains unclear whether calcineurin plays an important role at an early stage in isoproterenol-induced cardiac hypertrophy. 5 Isuzu Yamori, MD