Alloxan infused into the isolated perfused rat pancreas caused transient insulin secretion and permanent suppression of amino-acid-stimulated glucagon release. Alloxan poisoning also prevented subsequent induction of glucose-mediated insulin release and also prevented the inhibition of glucagon release by glucose. Glucose or 3-0-methylglucose infused simultaneously with alloxan protected the .alpha.- and .beta.-cell, allowing subsequent glucose inhibition of glucagon secretion and stimulation of insulin release. The alloxan effects were dose-related, the .alpha.-cell being 1/4 as sensitive to alloxan as the .beta.-cell. Alloxan and glucose suppression of amino-acid-stimulated glucagon secretion is independent of concomitant insulin secretion. Alloxan, like glucose, affects .alpha.- and .beta.-cells directly, stimulating the .beta.-cell and inhibiting the .alpha.-cell. Alloxan acts on a glucorecptor system with comparable physicochemical characteristics common to both cell types.