In cases of opioid-induced pain and neuropathic pain syndromes the successful use of NMDA-receptors antagonists like ketamine is reported. There is no widely accepted scheme of dosage of ketamine and few data exists for its oral use. Especially in home care settings parenteral application can be difficult. We report about 5 patients with difficult pain syndromes (1 under methadone substitution because of drug abuse and neuropathic cancer pain, 4 with opioid-induced pain and neuropathic pain syndromes). The patient with methadone substitution initially needed 300 mg ketamine per day intravenously and was changed to an oral dosage of 800 mg per day. With the 4 other patients we started out giving 1 mg/h ketamine i.v. and changed to an oral formulation with 25 mg 4 times daily. In one of these patients the change to an oral application failed. All in all 4 patients received oral ketamine successfully without the dosage needing to be raised over a period of a few month. NMDA-receptor antagonists are potential adjuvants in difficult pain syndromes. In 4 patients we describe a simple method of oral application with no side effects and good effectiveness over a long time. Further trials are required.