This study was carried out to determine clinical features, abnormalities on CT scan and MRI, and course in patients with HIV-I-related progressive multifocal leukoencephalopathy (PML). There were 14 patients with a presumptive diagnosis of PML among 500 HIV-I infected patients with neurological complaints, examined between September 1982 and May 1991 in the University Medical Centre in Amsterdam by a neurologist. In these 14 patients clinical features, imaging abnormalities and course of the disease were analysed retrospectively. All patients presented with progressive focal neurological abnormalities. Cerebrospinal fluid analysis revealed aspecific abnormalities in 5/13 patients. CT scanning of the brain showed hypodense areas in the white matter, without mass effect and with contrast enhancing in only one patient. MR Imaging of the brain showed high signal intensity areas in white matter and in gray matter (10/13), without mass effect, and with contrast enhancement in two. Specimens for neuropathological examination were obtained from 7 patients; in all these cases the diagnosis of PML was confirmed. In patients with AIDS a presumptive diagnosis of PML can be based on clinical features, brain imaging abnormalities and course. However neuropathological confirmation remains the gold standard. Usually the course in these patients was steadily progressive. Most patients died within one year.