The term memory effect refers to the phenomenon that B cell stimuli retain some of their insulinotropic effects after they have been removed. Memory effects exist for glucose and sulfonylureas. It is not known whether there is a B-cell memory for incretin hormones such as GLP-1. Eight healthy young volunteers were studied on four occasions in the fasting state. In one experiment, placebo was administered (a), in three more experiments (random order), synthetic GLP-1 (7-36 amide) at 1.2 pmol/kg/min was administered over a period of three hours. At 0 min, a bolus of glucose was injected intravenously (0.33 g/kg body weight). GLP-1 was infused from (b)-60 to 120 min,(c)-210 to-30 min, or (d)-300 to-120 min. Glucose (glucose oxidase), insulin, C-peptide, GLP-1, and glucagon (immunoassays) were determined. Statistical analysis was carried out by ANOVA and appropriate post hoc tests. GLP-1 plasma levels during the infusion periods were elevated to 89±9, 85±13, and 89±6 pmol/l (p< 0.0001 vs. placebo, 10±1 pmol/l). Glucose was eliminated faster (p< 0.0001), with an enhanced negative rebound (p= 0.014), and insulin and C-peptide increments were greater after intravenous glucose administration (p< 0.0001) if GLP-1 was administered during the injection of the glucose bolus, but not if GLP-1 had been administered until 120 or 30 min before the glucose load. There was a trend towards higher insulin concentrations (p= 0.056) five minutes after glucose with GLP-1 administered until-30 min before the glucose load. Glucagon was suppressed by exogenous glucose, but increased significantly (p= 0.013) during the induction of reactive hypoglycemia after glucose injection during GLP-1 administration. 1) No memory effect appears to exist for insulinotropic actions of GLP-1, in line with clinical data. 2) Reactive hypoglycemia causes a prompt rise in glucagon despite pharmacological circulating concentrations of GLP-1. 3) Similar studies should be performed in Type 2-diabetic patients, because exposure to GLP-1 might recruit dormant pancreatic B cells to become glucose-competent, and this might contribute to the overall antidiabetogenic effect of GLP-1 in such patients.