Phamacotherapy trials for cocaine abuse among methadone-maintained patients have typically reported negative findings as well as high rates of cocaine use during the trial. The contribution of motivational factors to these results is a potentially important, under investigated area. This article points out that some methadone-maintained patients may enter a trial for cocaine abuse with little desire for treatment, motivated primarily to continue receiving methadone or to avoid program sanctions for continued cocaine use. Participants in clinical trials may constitute a phase delaying discharge in a cyclic pattern of multiple treatment episodes. Testing a pharmacologic agent in a motivationally inappropriate sample may not provide a good estimate of the agent's effectiveness. In view of the important public health role that methadone maintenance programs play in preventing HIV transmission, and the subversion of this role by intravenous cocaine use, solutions to these problems are urgently needed. The authors suggest several possible approaches, including pre- and posttreatment motivation assessment, as well as the inclusion of psychosocial interventions that provide the context for the emergence of potential medication effects.