Natural killer (NK) cell activity against K562 cell targets and the distribution of T cell subpopulations were investigated in the peripheral blood of 25 patients affected by beta thalassemia major, 18 clinically healthy heterozygotes, and 25 age-matched normal subjects. It was found that thalassemia major patients display augmented levels of NK activity [specific lysis 41.9+ (se) 4.5%], while thalassemic carriers behave as normal controls [specific lysis 34.6+ (se) 3.5%]. The increase of NK function was neither related to the splenectomy nor to the siderosis, but rather to the age and the amount of blood units that the patients had received. An imbalance of circulating T subsets with the helper/suppressor cell ratio significantly diminished (p < 0.001) was also detected in homozygotes but not in carriers. The finding that NK function is enhanced in homozygous beta thalassemia might be of clinical interest in assessing the risk of development of malignancies in these patients.