Monoclonal antibodies (OKT series) have been used to investigate possible modifications of T lymphocytes and T lymphocyte subsets in 65 multiply transfused β-thalassemia patients. No significant difference was observed in percentage and absolute number of OKT3-, OKT4-, and OKT8-positive cells when compared to controls. A subgroup of patients (10 patients, 15.3%), however, could be selected who showed a reversal of OKT4/OKT8 ratio. These patients did not differ from the others as to age, number of transfusions, frequency of splenectomy, ferritin levels, hepatitis B markers, chronic liver disease incidence, and numbers of B lymphocytes and natural killer cells. The features distinguishing this group from the remaining patients were: (1) decreased mitogen responsiveness; (2) early age when first transfused; (3) high incidence of males (90%). Immunological investigation was done in 2 occasions, 1 year apart, but no significant modification was observed in these patients. These findings suggest that in β-thalassemia patients transfusion therapy started very early in life may be responsible for persistent immunological modifications. The susceptibility to such modifications might be greater in males.