Cytomegalovirus (CMV) is an increasingly important opportunistic pathogen in patients with HIV infection and advanced immune deficiency. Neurological complications due to CMV cause significant morbidity but may be treatable with specific anti-viral therapy; cerebral mass lesions are not a generally recognised manifestation. We report two patients with CMV encephalitis presenting as a cerebral mass lesion, with simultaneous occurrence of a pleuro-pulmonary mass also caused by CMV in one case, and with concurrent polyradiculomyelopathy in the other. The spectrum of previously reported clinical and radiological features of CNS involement in AIDS is discussed CMV should be considered in the differential diagnosis of cerebral mass lesions in patients with HIV infection and severe immune deficiency so that anti-Viral therapy can be rapidly deployed.