The effect of enteric factors on immunoreactive insulin (IRI) and glucagon (IRG) release from isolated islets of Langerhans of the rat was studied. Glucagon caused slight stimulation of IRI release but only at the high concentration of 10 μg. per milligram, and its effect was seen only at aconcentration of glucose of 150 mg. per 100 ml. but not at 30 or 300 mg. per 100 ml. Crude alcohol extracts of intestinal mucosa containing IRG were ineffective in promoting IRI release. Purified pancreozymin and secretin, and a gastrin preparation failed to cause an increase in release of IRI and IRG. Altering the glucose concentration in the media resulted in opposite effects on the release of IRI and IRG; also, IRI release was stimulated by tolbutamide and inhibited by diazoxide, implying that the isolated islet hormone releasing mechanisms are intact. It is suggested that enteric factors may mediate their effects on IRI and IRG release in vivo by indirect means.