MAIDS is a retrovirus-induced immunodeficiency syndrome of mice characterized by progressive lymphoproliferation and immunodeficiency. Affected mice also exhibit neurologic defects characterized by impaired learning associated with histologic lesions. Induction of disease requires only expression of an unusual Gag protein encoded by a defective virus. Abnormal cytokine signaling contributes to disease through intracellular pathways that are poorly defined in either lymphocytes of the brain. Studies have emphasized that understanding interferon signaling patterns will be crucial for uncovering the basis for both neurologic and immunologic defects. For example, mice unable to express interferon gamma develop accelerated neurologic disease but immunologic abnormalities are delayed.