Islet amyloid may have a pathological role in the development of Type 2 (non-insulin-dependent) diabetes mellitus. The prevalence of islet amyloid has been investigated on post-mortem pancreatic tissue from both diabetic and non-diabetic Pima Indian subjects who had previously been assessed by oral glucose tolerance tests. Islets were examined for amyloid deposits and for cellular immunoreactivity to pancreatic hormones and islet amyloid polypeptide, the constituent peptide of islet amyloid. Twenty of 26 diabetic subjects (77%) had islet amyloid, compared with one of 14 non-diabetic subjects (7%). Twelve of the diabetic subjects (46%) had amyloid in more than 10% of their islets, whereas only 4% of islets were affected in a single non-diabetic subject. Positive immunoreactivity for islet amyloid peptide was present in the islet amyloid and in islet cells in 54% of the diabetic and 50% of the non-diabetic subjects. Islet amyloid in diabetic Pima Indians may indicate a primary Beta-cell defect which interacts with insulin resistance to produce diabetes, or may develop as a result of Beta-cell dysfunction induced by insulin resistance and hyperglycaemia.