We reported a 50-year-old woman with a history of mixed connective tissue disease. She had two episodes of meningitis-like symptoms after taking famotidine and tiquizium bromide for treatment of gastric ulcer. From CSF findings (elevated pressure, increase of protein, polymorphonuclear pleocytosis, negative culture) and result of famotidine challenge test, we diagnosed her as a drug induced aseptic meningitis. Because she had taken tiquizium bromide several times previously without any side effects, we concluded that famotidine was a causative drug. She was recovered without sequelae within a few days following cessation of these drugs. This is the first report of H2-blocker induced aseptic meningitis. When we encounter a patient with aseptic meningitis who presents polymorphonuclear pleocytosis in CSF, we should suspect drug induced aseptic meningitis and take a history of drug medication including H2-blocker.