Polymorphisms in the ABCB1/MDR1 gene coding for P-glycoprotein may account for individual differences in mefloquine accumulation in the brain, which in turn have been proposed to mediate mefloquine’s treatment efficacy with progressive multifocal leukoencephalopathy and might similarly influence individual differences in the behavioral effects of mefloquine exposure. Here, ABCB1 is linked to progressive multifocal leukoencephalopathy.