To assess the possible role of pancreatic monoamines in the impaired insulin secretion of the fasting state, in vitro pancreas incubation studies were performed using pancreas tissue obtained from fed, fasted and fasted—plusreserpine— treated hamsters. Reserpine was used to deplete pancreatic monoamine content. The pancreatic insulin content was similar in the three groups. Basal insulin secretion and insulin secretion stimulated by glucose, acetylcholine and tolbutamide was decreased by fasting when compared to the fed state. This impairment in insulin secretion from pancreas obtained from fasted animals was partially prevented by concomitant reserpine administration. The impairment in insulin secretion from pancreas of fasted animals was also partially prevented by α–methyl tyrosine or para—chlorophenylalanine. Alpha—methyl—tyrosine and para—chlorophenylalanine did not alter insulin secretion from the pancreas of fed hamsters. These studies suggest that pancreatic monoamines may play a role in the decreased insulin secretion of the fasting state. (Endocrinology92: 1469, 1973)