We describe a 9-year-old white boy with systemic juvenile rheumatoid arthritis (JRA) who developed pancytopenia and hypersplenism at the age of 13 years. He underwent splenectomy and 3 years later he developed Coombs' positive hemolytic anemia, alopecia, juvenile warts, and multiple bacterial infections. At that time, investigations were compatible with severe hypogammaglobulinemia associated with common variable immunodeficiency. Concomitantly with this condition he experienced complete remission of his inflammatory arthritis. Immunologic studies of B and T lymphocyte function showed that the number of circulating T and B lymphocytes were normal, while T cell function was depressed, as evidenced by markedly reduced proliferative responses to mitogens and antigens, and ability to mediate B cell help. In addition, his circulating B cells were unable to secrete IgM or IgG. He also exhibited anergy to intradermal challenge with a battery of common antigens. The literature dealing with this clinical association is reviewed, and possible immunologic mechanisms involved are discussed.