Objectives.It is important that health measures are both reliable and responsive to clinical change. The aim of this study was to assess the reliability and responsiveness of the physical, mental, and social health scales of the Duke Health Profile (DUKE).Methods.Impotent males self-administered the Duke Health Profile before and during treatment with alprostadil for erectile dysfunction during a 19-month period. Subjects were 490 patients in the United States and 583 patients in 12 other countries. Each of the three basic Duke Health Profile scales has only five items, and each is heterogeneous because each measures more than one health concept.Results.Cronbach's alpha reliability estimates were: physical health, 0.68 for United States and 0.64 for other countries; mental health, 0.62 and 0.52, respectively; and social health, 0.53 and 0.47, respectively. Alprostadil was expected to improve mental health primarily, and results of the study were consistent with this hypothesis. For example, at approximately 14 months from therapy onset, mental health improved for patients both in the United States (standardized response mean, SRM, = 0.17) and other countries (mean SRM = 0.30), whereas physical health worsened in the United States and was unchanged in other countries, and social health was unchanged in the United States and improved in other countries. Maximum responsiveness was shown for mental health in the other countries, where the mean standardized response means at four follow-ups during a 19-month period were 0.11, 0.21, 0.30, and 0.36.Conclusions.This study provides support for the responsiveness of the Duke Health Profile mental health scale.