In adult rats injected intravenously with streptozotocin (STZ: 20 or 40 mg/kg body wt) and examined 13 days later, the secretory response of the perfused pancreas to D-glucose is impaired. A paradoxical inhibition of insulin release is even observed in the perfused pancreas of rats given the high STZ dose. When pulses of succinate monomethyl ester (SAM: 60 mg) were administered intraperitoneally three times a day for one week from the 6th to 12th day after STZ injection, no obvious difference in insulin output from the perfused pancreas stimulated with either D-glucose or SAM was observed between SAM-treated and untreated rats first injected with the low STZ dose. However, in rats first injected with the high STZ dose, the secretory response to SAM was higher in SAM-treated than untreated animals. These findings raise the view that suitable non-glucidic nutrient secretagogues might improve, in a long term manner, the secretory potential of the endocrine pancreas in animal models of diabetes characterized by a preferential impairment of the B-cell response to D-glucose.