Reversible posterior leukoencephalopathy syndrome (RPLS) is an uncommon entity related to multiple and different pathologies, the most common being hypertensive crisis. It is believed to be secondary to the breakdown on the blood-brain barrier. At the beginning, it is undistinguishable from other leukoencephalopathies. However, the disappearance of brain lesions after removal of the potential cause, establish the differential diagnosis with other leukoencephalopathies. We present the case of an HIV-infected patient with a RPLS related to a hypertensive crisis short after the initiation of indinavir-containing highly active antiretroviral therapy. Once blood pressure was controlled and indinavir replaced by nelfinavir, white matter lesions at magnetic resonance imaging disappeared. The clinical and radiologic evolution excludes other diagnosis as progressive multifocal leukoencephalopathy and points indinavir as a potential hypertension-inducing agent in HIV-infected predisposed subjects.