It has become increasingly common for parents of children with autism to supplement behavior analytic interventions with therapies that have not yet been subjected to adequate scientific scrutiny. When caregivers elect to use unproven therapies despite advice to the contrary, practitioners should employ the methods of applied behavior analysis to experimentally evaluate the outcomes. Controlled evaluations of unproven therapies can be challenging, however, particularly when ongoing behavioral services are supplemented with biomedical interventions. This paper describes the methods and results of a behavior analytic evaluation of hyperbaric oxygen therapy, an unproven intervention that has been growing in popularity over the past several years. Three young children with autism participated. No benefits of the therapy were evident beyond those obtained through the behavioral intervention alone. Considerations for conducting this type of research are highlighted, along with suggestions for practitioners.