Guinea pigs injected with streptozotocin showed temporary hyperglycemia and retardation of body growth. One month after streptozotocin injection the islets of Langerhans of these animals consisted mainly of A2-cells. Compared to the control animals the nuclei of the B- and A1-cells were increased in size. Microrespirometric analyses of the isolated islets from streptozotocin-treated animals showed that the endogenous respiratory rate was in the same range as that of islets from the controls. Addition of D-glucose to the incubation medium caused a stronger stimulation of the oxygen uptake in the control islets than in the islets from the streptozotocin-treated animals. However, when the medium was supplemented with succinate the islets from the latter animals had a higher oxygen uptake. The predominance of A2-cells in these islets supports the idea that the results are representative mainly for this cell type. The results may thus reflect a fundamental difference in the metabolism between the Band A2-cells. 1 Supported by grants from the Swedish Medical Research Council (B70-2297-03; B70-109-06B), the United States Public Health Service (AM-12535), Nordisk Insulinfond and Svenska Diabetesförbundet. The streptozotocin was kindly supplied by Dr. W. Dulin, the Upjohn Company, Kalamazoo, U.S.A.