The clinical and immunologic findings in an elderly woman with thymoma and immunoglobulin deficiency in whom cytomegalovirus (CMV) encephalitis developed are described. The patient had absent serum immunoglobulins and no circulating immunoglobulin-bearing lymphocytes. Complement receptor-bearing lymphocytes were present in the peripheral blood, and circulating T lymphocyte numbers were within normal limits. She was anergic to a battery of skin test antigens, and her lymphocytes in vitro showed a selective unresponsiveness to CMV antigen while responding normally to phytohemagglutinin and streptokinase. The course of the encephalitis was progressive with quadriplegia, aphasia and coma developing within six months of onset of symptoms. This is the fifth reported case documenting an association between CMV infection and the syndrome of thymoma with immunoglobulin deficiency, but the first report of fatal CMV encephalitis in a patient with thymoma and immunoglobulin deficiency.