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To assess whether trial participants who ceased efavirenz (EFV) because of neuropsychiatric events had elevated plasma concentrations, we performed a retrospective case–control study. EFV levels were measured by high-performance liquid chromatography in stored plasma from 35 cases and 75 matched controls. All had taken EFV for at least 4 weeks. Median EFV concentrations did not differ (P = 0.77). Measurement of EFV levels in plasma collected at variable times after the last dose did not predict central nervous system intolerance.