Lymphocyte subsets in 53 patients with acute rheumatic fever and 78 patients with chronic rheumatic heart disease were compared with 20 normal control subjects and 39 patients suffering from uncomplicated streptococcal pharyngitis to obtain information about the pathogenesis of the disease. Twenty patients with rheumatic fever were followed for 24 weeks to evaluate changes occurring over the course of the disease. Total leukocyte and lymphocyte counts were increased in patients with rheumatic fever and to a lesser extent in those with rheumatic heart disease, when compared with controls. The difference between the two groups was significant. Patients with acute rheumatic fever had an increased number of B cells and a smaller increase in total T and T-helper-inducer (CD-4) cells. The proportion of B cells increased, while that of T-suppressor-cytotoxic (CD-8) cells fell. An increased number and proportion of B cells was also seen in patients with rheumatic heart disease. Total T and T-helper lymphocyte percentages and numbers were significantly higher in patients with rheumatic fever compared with those of patients with rheumatic heart disease. Follow-up studies at 6, 12, and 24 weeks revealed no significant differences from the entry point studies, although there was a trend toward reduction in the degree of derangement from normal values. Patients with uncomplicated streptococcal pharyngitis, however, did not show perturbations in the T-cell and T-subset counts. Our study suggests that the immunoregulatory defect in acute rheumatic fever is characterized by a relative reduction of suppressor T cells with an absolute increase in helper T cells and B cells, resulting in an increased cellular as well as humoral immune response.(ABSTRACT TRUNCATED AT 250 WORDS)