Two human immunodeficiency virus seropositive patients with progressive multifocal leukoencephalopathy (PML) exhibited a dramatic though incomplete recovery of neurologic function and have survived for more than 30 months since the onset of symptoms. PML was the initial manifestation of the acquired immune deficiency syndrome (AIDS) in both patients, though other opportunistic infections have subsequently supervened in one. Brain tissue from both patients obtained by stereotactic biopsy showed the typical features of PML, but was also characterized by an unusually prominent inflammatory response. Neurologic improvement did not appear to correlate with clinical or laboratory measurements of immunologic improvement. One patient continued to display neurologic recovery despite the development of other opportunistic infections. Though atypical, PML in AIDS may be associated with prolonged survival.