Patients with agammaglobulinemia are particularly susceptible to chronic enteroviral infections of the central nervous system. Data on 42 patients were obtained by literature review, communications with other physicians, and personal experience. Thirty-eight patients had congenital immunodeficiencies, most frequently X-linked agammaglobulinemia. Most patients who could be assessed were receiving maintenance therapy with intramuscular γ-globulin before their enteroviral infection. Seven patients had not been recognized as hypogammaglobulinemic before the onset of infection. The commonest pathogens were echoviruses (37 of 41 cases), especially type 11 (11 cases). Thus far, four patients have had sequential or simultaneous infections with a second enteroviral serotype. Other features of the disease have included weakness, lethargy or coma, headaches, hearing loss, seizures, ataxia, and paresthesias. Some patients have also had nonneurologic manifestations of chronic enteroviral infection, including fever, the dermatomyositislike syndrome, edema, rashes, and hepatitis. Treatment has consisted primarily of antibody administration, either in intravenous immunoglobulin preparations or in immune plasma. Twelve patients have received intraventricular immunoglobulinthrough reservoir devices; six of these 12 have improved substantially, as judged by clinical criteria.