Some patients in methadone maintenance treatment programs have substantial difficulty adjusting to changes in methadone formulation and shifts in other program policies. Clinicians can benefit from the ability to identify individuals who are "at risk" for methadone formulation and other change intolerance. By studying a cohort of 177 patients who were receiving methadone maintenance in a program that changed methadone dispensing formulations, this study revealed significant differences between two underlying patient groups (i.e., change tolerant or intolerant). These patients were distinguished by personal characteristics prior to the formulation change and methadone dose level shifts after the formulation change. Change-intolerant patients experienced formulation-related narcotic withdrawal whereas change-tolerant patients adapted to the new medication format. Gender, treatment history, and methadone abuse were three sociodemographic variables that significantly predicted patients who were intolerant to a methadone formulation change. These findings suggest the need for more research, including plasma and metabolic studies, to clarify the potential biological effects of changes in methadone formulations. In addition, the treatment implications for patients who experience change intolerance are discussed.