Acute toxic methemoglobinemia is an infrequent complication of the use of various drugs. Severe methemoglobinemia is very often fatal. Methylene blue is an effective drug in the treatment of methemoglobinemia patients. However, failure to respond to methylene blue has been described in patients with sulfhemoglobinemia, chlorate poisoning, and glucose-6-phosphate dehydrogenase deficiency. It is even possible that hemolysis may occur due to methylene blue treatment itself. We encountered a case of a 71-year-old woman who developed methemoglobinemia caused by alprazolam intoxication. She presented with hemolytic anemia and did not respond to methylene blue. In spite of concerted N-acetylcysteine therapy, the hemolytic anemia became aggravated and the patient died eleven days after intoxication.