Thirty-nine consecutive patients with beta-thalassemia major and iron overload were studied by ultrasonography and serum pancreatic enzyme determination to assess the frequency and characteristics of pancreatic damage in this condition. The results were compared with those of a matched group of healthy controls. Most of the thalassemic patients had a markedly increased echogenicity of the pancreas and decreased size of the gland (p < 0.001 for both features as compared with controls). Both echogenicity and decreased size of the gland were significantly correlated (p < 0.001) with patient age and duration of transfusional therapy. Serum concentrations of trypsin and lipase were significantly lower (p < 0.02) in patients than in controls. The lowest enzyme values were found in older patients with longer duration of transfusional therapy, who also had the most marked sonographic changes. The results suggest that the exocrine pancreas is structurally and functionally damaged in the majority of thalassemic patients with iron overload.