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Meningitis is a potentially life threatening medical emergency. Psychotic behavior may be a presenting feature in patients with meningitis. We aimed to determine the value of various clinical and laboratory features at ruling-out meningitis in the patient presenting with a first-episode of psychotic behavior.Medical records of 159 subjects presenting to a tertiary academic hospital over a 6-month period with one or more psychotic features for the first time were prospectively gathered. Pathological cerebrospinal fluid findings as well as clinical and other laboratory findings were tabulated and discussed retrospectively.Cerebrospinal fluid was obtained in 153/159 (96.2%) subjects. Meningitis was confirmed in twenty-eight (18.3%) subjects. Of these, a) one or more clinical feature of meningitis (headache, neck stiffness, photophobia or focal neuropathy) was present in 21 subjects (75.0%), b) visual hallucinations in 15 subjects (53.6%), c) pyrexia >37.5 °C in 7 subjects (25.0%), d) CRP >10 mg/L in 21 subjects (75.0%), e) HIV seropositive status in 19 subjects (67.9%) and f) an absence of illicit substances on urinalysis in 23 subjects (82.1%). Various combinations of these variables, where the presence of ≥1 variable was regarded as positive, were unable to rule-out meningitis in all study subjects.The absence of these six parameters; alone or in various combinations, was unable to rule-out meningitis in all patients presenting to our ED with a first-episode of psychotic behavior. When the underlying etiology of psychotic behavior is not obvious, the clinician should adopt a low threshold to perform a lumbar puncture.