The authors investigated the spectrum of radiologic findings in a large series (n = 47) of patients seropositive to human immunodeficiency virus (HIV) 1 and with pathologically proved progressive multifocal leukoencephalopathy, to determine the characteristic imaging pattern of the disease. Thirty-six computed tomographic (CT) scans and 29 magnetic resonance (MR) imaging studies obtained in the 47 patients were retrospectively reviewed and correlated with pathologic and clinical findings. Contrast agents were used in 32 CT procedures and 13 MR imaging studies. Lesions typically were hypoattenuating on CT scans and were characterized by areas of increased signal intensity without mass effect on dual-echo MR images. Lesions most often involved periventricular and subcortical white matter in parietooccipital or frontal lobes. Fifteen patients had posterior fossa lesions, and disease was limited to the posterior fossa in two. Lesions were also in the corpus callosum (seven patients), thalamus (eight patients), and basal ganglia (seven patients). In comparison with CT, MR imaging demonstrated greater sensitivity for the extent and number of lesions.