The purpose of this study was to evaluate cellular immune responsivenes.s in patients with acute rheumatic fever (ARF). Peripheral blood lymphocytes were obtained for culture from patients who had ARF within the past 2-3 months. No patient was receiving steroids at the time of the study. Peripheral lymphocytes were also obtained from normal control individuals.Lymphocyte cultures were maintained for 7 days in minimum essential medium with 10% fetal calf serum in a 5% CO2 environment. Cellular responsiveness was checked concomitantly with pokeweed mitogen and/or phytohemagglutinin. Mixed-lymphocyte cultures were studied between patients with ARF and between patients with ARF and normal controls. Normal responses were arbitrarily defined as a threefold increase over baseline counts.ARF cells were capable of stimulating other ARF cells in only three of 14 instances and were able to stimulate control cells in only three of 11 studies. Conversely, ARF lymphocytes were capable of being stimulated by control normal cells in five of 10 experiments. Thus decreased cellular responsiveness and abnormalities in cellular immunity are present in many patients with ARF, since lymphocytes from patients with ARF are usually incapable of stimulating normal or other ARF cells. However, ARF cells are capable of being stimulated by normal control cells in 50% of studies performed. CLOSE HISTOLOGIC inspection of the microscopic cardiac lesions in acute rheumatic fever, such as areas of acute myocarditis or Aschoff bodies themselves, often shows prominent cellular infiltrations with small and medium-sized lymphocytes. It is surprising, therefore, that more attention has not been directed to a study of circulating lymphocytes in individuals afflicted with acute or subacute rheumatic fever. There is indeed a voluminous literature dealing with various