The use of mefloquine for malaria prophylaxis has been hampered by the drug's adverse effects. Foremost among the latter are neuropsychiatric adverse effects such as dizziness, vivid dreams, epilepsy and psychosis. Recent evidence from studies in mice has implicated the lack of P-glycoprotein at the blood-brain barrier as the cause of these adverse effects. The authors present the case of a 60 year-old man who was hospitalized for psychosis following ingestion of mefloquine for malaria prophylaxis. Genetic studies have found polymorphism at the MDR1 gene with genotypes 3435TT and 2677TT which underlie high levels of mefloquine in the brain.