Frequent transfusions improve the general well being in patients with beta-thalassemia major but carry the risk of iron intoxication including the development of diabetes mellitus. Of 22 patients with beta-thalassemia major (age 3-17 years) only 3 had a normal oral glucose tolerance. The remainder had either borderline or moderately pathological glucose curves. The mean glucose concentration was increased, and the mean insulin concentration and insulin/glucose ratio were diminished. In contrast to the oral test, the i.v. glucose tolerance test gave pathological results in only 2 of 16 patients tested. The i.v. glucose test thus may be less selective than the oral test. The mean insulin concentration was lower also after intravenous glucose, but the early insulin peak was preserved. Arginine infusion led to a normal insulin and growth hormone release. This moderate impairment of insulin release found in most of the patients leaves the hope that an efficient chelating therapy scheme might reverse beta-cell dysfunction.