We reviewed cases of cytomegalovirus (CMV) infection of the central nervous system (CNS) that initially masqueraded as tumors in 37 of 543 consecutive patients infected with human immunodeficiency virus (HIV) and CMV who were seen at the Pasteur Institute Hospital and Saint-Louis Hospital (Paris) between 1992 and 1994. We detail the clinical features of three patients who presented with ring-enhanced space-occupying lesions mimicking CNS tumors. They were all profoundly immunodepressed (mean CD4 cell count, 13/mm3). Magnetic resonance imaging (MRI) showed enlargement of the spinal cord in one case, consistent with a space-occupying lesion and showing gadolinium enhancement; in the other two cases, ring-enhanced mass lesions were seen in the cerebral hemispheres. In all three cases marked edema and a mass effect were present. Image-guided stereotactic biopsies confirmed the diagnosis of CMV infection. The three patients' conditions improved with specific therapy. MRI showed enhanced focal intraparenchymal lesions consistent with marked focal necrosis, probably related to the severity of immunodepression, as HIV infection had been diagnosed several years previously. CMV infection should be considered as a cause of ring-enhanced space-occupying mass lesions in patients with HIV-1 infection. Earlier identification of these unusual tumorlike forms of CMV infection by means of MRI should result in improved outcome.