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People dependent on heroin who do not respond to other treatments have been treated by a combination of heroin and methadone. In this Policy Forum, Bammer et al. argue that the debate about the merits of this treatment could be substantially informed by clinical trials that meet rigorous scientific standards. Because of the complexities of working with the dependent user population and the social and individual risks associated with this potential treatment, a series of interlocking trials with various designs and control groups are essential, and social impacts must also be monitored. Heroin will always be a second- rather than first-choice treatment, and if trials show that it has any value, the political outcome will be medicalization, not legalization.