The in vitro inhibition of insulin release by alloxan (20 mg/100 ml) in collagenase isolated rat islets is preferentially prevented by .alpha. D-glucose at a concentration of 1.0 mg/ml, while at a higher anomer concentration (1.5 mg/ml) both .alpha. and .beta. D-glucose provide equal protection. The ability of .alpha. D-glucose compared with .beta. D-glucose to stimulate insulin release, in vitro, showed a similar dose-related response, as observed in the alloxan protective studies. Although both .alpha. and .beta. D-glucose compete with mutorotated D-glucose for transport into islet cells, neither anomer produced a significantly different degree of inhibition in the transport process. The shared .alpha. stereospecificity for D-glucose in protection against alloxan and in stimulating insulin secretion in these in vitro studies suggest a common site of interaction which may be involve the .beta.-cell membrane.