A severe withdrawal syndrome occurred in a patient after oxazepam 10 mg bid was substituted for diazepam 5 mg bid. The onset of symptoms was consistent with the rate of decline of diazepam and its active metabolite, desmethyldiazepam. Reintroduction of diazepam produced prompt symptom remission. This report and others suggest the need for caution when substituting a short-acting drug for a long-acting one, even when usual doses of each are used. The chronic use of benzodiazepines for eight months or longer prior to substitution or withdrawal appears to place the patient at a higher risk of incurring withdrawal phenomena. Slow and careful tapering of drug is required in such patients to reduce the risk of withdrawal symptoms.