In female rats aspirin-induced gastrin mucosal damage was increased and glycoprotein synthesis decreased by fasting and by insulin administration. Glucose added to the drinking water during the fasting period reduced mucosal damage and increased glycoprotein synthesis to control levels. Alloxan diabetes did not affect mucosal damage or glycoprotein synthesis. Alloxan diabetes plus insulin restored blood glucose levels to normal, and susceptibility to aspirin damage and glycoprotein synthesis were also normal. Alloxan diabetes plus fasting restored blood glucose levels to normal but increased aspirin-induced mucosal damage and reduced glycoprotein synthesis. In vitro incubation of gastric mucosal homogenates showed that diburyryl cyclic AMP and theophylline inhibited glycoprotein synthesis but dibutyryl cyclic GMP had no significant effects. The importance of an adequate supply of glucose to the gastric mucosa and the effects of cyclic nucleotides on glycoprotein synthesis are discussed.