Glyco-metabolic status was evaluated in 29 pubertal homozygous thalassaemics aged from 17 to 42 years and in 12 age-matched healthy subjects. Diagnosis of diabetes mellitus was assessed in 4 patients (13.8%), who became diabetic after the age of 18 years. With respect to controls non-diabetic patients exhibited significantly higher fasting plasma glucose levels and more sustained glycemic responses to oral glucose tolerance test, whereas their overall insulin output was significantly lower. Moreover non-diabetic thalassaemic patients showed a clear reduction of both beta-cell function and insulin resistance indices (HOMA model). In conclusion our data show a high prevalence of diabetes but do not support the existence of an insulin resistant status in thalassaemia major, at least in adulthood.