The imaging studies of 16 patients with acquired immunodeficiency syndrome (AIDS) and proved primary central nervous system (CNS) lymphoma were reviewed. All studies included computed tomography (CT); six also included magnetic resonance (MR) imaging. A periventricular lesion was seen in 50% of patients. At least one such lesion exhibited subependymal spread or ventricular encasement in 38%. One-third of lesions in three of five patients who underwent nonenhanced CT were hyperattenuating. Five lesions were at least in part hypointense on T2-weighted MR images. The specificity of these findings was evaluated with a similar review of the imaging studies in 28 patients with AIDS and proved toxoplasmosis. Only 3% of lesions were periventricular. None exhibited subependymal spread or encasement. None were hyperattenuating on nonenhanced CT scans. Similar findings in other CNS lesions in AIDS patients could not be found in the literature. A focal enhancing mass with subependymal spread on CT or MR images and hyperattenuation at nonenhanced CT were the most reliable features in distinguishing between primary CNS lymphoma and toxoplasmosis in AIDS patients.