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1. The possible significance of the insular sorbitol pathway in glucose-induced insulin release was investigated. 2. Glucose, but neither fructose nor galactose, stimulated sorbitol synthesis by isolated islets. Aldose reductase inhibitors such as 2,4-dimethylglutaric and 3,3-tetramethylene glutaric acid abolished the glucose-induced sorbitol formation, but failed to affect glucose-induced insulin release. About 75% of the sorbitol formed by the islets was recovered in the incubation medium, the efflux of sorbitol occurring independently of insulin release. Exogenous fructose and sorbitol exerted a modest insulinotropic action characterized by a shift to the left of the sigmoidal curve relating insulin release to glucose concentration. The relative insulinotropic potency of glucose (100%), fructose (16%) and sorbitol (7%) paralleled their rate of oxidation by the isolated islets. 3. These data suggest that metabolism through the sorbitol pathway plays little role in the process of glucose-induced insulin release, although exogenous sorbitol exerts a modest insulinotropic action. [ABSTRACT FROM AUTHOR]