Increased interest in addiction psychopharmacology has raised unique methodologic issues in the design, conduct, and analysis of outcomes in clinical trials of therapeutic agents for drug dependence.This article summarizes issues raised at a meeting in Palo Alto, California, on November 4, 1996, that was sponsored by the Medication Development Division of the National Institute on Drug Abuse and the Department of Veterans Affairs Cooperative Studies Program to discuss the methodologic issues in clinical trials of cocaine pharmacotherapy. (J Clin Psychopharmacol 1999; 19:246-256)