Ibuprofen is a common nonsteroidal antiinflammatory drug that is the most frequent cause of aseptic meningitis induced by drugs. The incidence of this type of aseptic meningitis is increasing, mainly among patients with underlying autoimmune connective tissue disorder, but also among healthy people. We report 2 patients with recurrent meningitis caused by ibuprofen mimicking bacterial meningitis: the first patient a woman with dermatomyositis and the second patient a previously healthy woman who developed autoimmune thyroiditis a few months later. We then review 71 episodes of ibuprofen-related meningitis in 36 patients reported in the literature. Twenty-two patients (61%) presented with an autoimmune connective tissue disorder, mainly systemic lupus erythematosus, and 22 (61%) had recurrent episodes. Most episodes consisted of an acute meningeal syndrome with a predominance of neutrophils in cerebrospinal fluid (CSF) in 72.2% of episodes and elevated protein in the CSF, so the clinical presentation of this type of aseptic meningitis may be quite similar to that of acute bacterial meningitis. CSF glucose levels are usually normal, which may help to differentiate between these 2 types of meningitis. In some cases the clinical presentation is that of meningoencephalitis with neurologic focal deficits. Although based on the close relation between the administration of ibuprofen and the onset of symptoms, especially if previous episodes have occurred, the diagnosis of ibuprofen-induced aseptic meningitis is a diagnosis by exclusion. If the clinical picture is compatible with bacterial meningitis, empirical antibiotic therapy must be administered until negativity of cultures and other microbiologic tests is determined. Rechallenge to ibuprofen reproduces the symptoms and confirms the diagnosis, but is usually not advised. Whatever the clinical presentation, physicians must consider the possibility of ibuprofen-related meningitis or meningoencephalitis in patients taking ibuprofen, especially if they are suffering from an autoimmune connective tissue disorder. On the other hand, we think it would be appropriate to screen for autoimmune disease in previously healthy patients diagnosed with ibuprofen-related meningitis or meningoencephalitis. Finally, we propose that meningitis due to ibuprofen be included in the list of causes of recurrent aseptic meningitis.