Difenoximide is a water insoluble derivative of diphenoxylate, a chemical congener of meperidine. Difenoximide has been shown to have a greater ability than methadone to suppress opiate withdrawal in addicted mice and it has produced less physical dependence than morphine and methadone in laboratory animals. Since diphenoxylic acid is the major metabolite of both difenoximide and diphenoxylate, it is assumed that difenoximide will have essentially the same dependence liability and long-term toxicologic effects as those of diphenoxylate. Difenoximide has been given to human volunteers and it showed antidiarrheal action without side effects. Difenoximide appeared to be a potentially useful agent for ambulatory narcotic detoxification. The only significant side-effect was constipation.