Development of spontaneous diabetes has been monitored in individual Macaca nigra. In this study, pancreatic biopsies were taken, islets were assessed morphologically, and results were related to the metabolic/clinical status. A biopsy or autopsy sample was obtained 4 to 10 years later, and the islet morphological state was again related to the metabolic/clinical status. Metabolic deterioration was correlated to the islet lesion, in which there was gradual loss of islet secretory cells and concurrent amyloid deposition. As nondiabetic monkeys with 0 to 3% islet amyloid progressed up to 20 to 40% amyloid, the insulin secretion and glucose clearance were both decreased (p less than or equal to 0.01), and the glucose and glucagon levels increased (p = 0.05). Impaired monkeys progressed to overt diabetes when islet amyloid exceeded 50 to 60%. Diabetic monkeys developed hyperglycaemia, along with impaired insulin secretion and glucose clearance (p less than 0.01). Loss of islet cells results in metabolic deterioration. The lesion precedes development of overt diabetes in Macaca nigra.