To test the feasibility of conducting a definitive randomized controlled trial of dexamphetamine substitution for amphetamine dependent people and provide preliminary data. An open, two-group pre-post randomized controlled trial. Forty-one long-term, dependent amphetamine users seeking treatment. Twenty subjects were offered weekly counselling. Twenty-one subjects were, in addition, prescribed up to 60 mg dexamphetamine daily. Immunoassay and mass spectrometric urinalysis techniques were used to identify the presence of amphetamine and methylamphetamine in urine. The Opiate Treatment Index and Severity of Dependence Scale were used to collect pre- and post-self-report data. Subjects were screened using the Composite International Diagnostic Interview. Reduced street amphetamine use and amphetamine dependence was observed both in subjects prescribed dexamphetamine and subjects receiving counselling only. Treatment subjects appeared more likely to attend counselling. A definitive randomized controlled trial of dexamphetamine substitution using the techniques and instruments piloted in this study is feasible. Users appeared to be attracted and retained in substitution treatment. The intervention also appeared to be acceptable to clinicians.