Intravenous infusions of glucagon-like peptide 1 (GLP-1) [7–36 amide] are glucose-dependently insulinotropic and glucagonostatic and normalize plasma glucose concentrations in non-insulin-dependent diabetic patients. It was the aim of this study to investigate whether subcutaneous GLP-1 [7–36 amide] also has an influence on insulin and glucagon secretion, and which doses are required for significant effects. Therefore, eight healthy volunteers (24±2 years, body mass index [BMI] 21.9±2.3 kg/ m2) were studied in the fasting state on five occasions in randomized order. Placebo (0.9% NaCl with 1% human serum albumin) or GLP-1 [7–36 amide] in doses of 0.15, 0.5, 1.5 or 4.5 nmol/kg body weight (volume 1 ml or, at the highest dose, 2 ml) was administered subcutaneously. An intravenous glucose bolus (0.33 g/kg body weight) was injected 30 min later. Blood was drawn for the measurement of glucose, insulin, C-peptide, GLP-1 [7–36 amide], and glucagon using specific radioimmunoassays. There were dose-related increments in GLP-1 [7–36 amide] concentrations (p<0.0001). However, basal values were reached again after 90–120 min. Before glucose administration, insulin (p<0.0001) and C-peptide (p<0.0004) increased, whereas glucagon (p = 0.0018) and glucose (p<0.0001) decreased in a dose-dependent manner. After glucose stimulation, integrated increments in insulin (p=0.0007) and C-peptide (p=0.02) were augmented and kG-values increased (p<0.0001) in a dose-related fashion. The extent of reactive hypoglycaemia was related to the GLP-1 [7–36 amide] dose. With the highest GLP-1 [7–36 amide] dose, at the time of peak plasma concentrations, most volunteers felt unwell, and nausea and vomiting were observed in four subjects. In conclusion, subcutaneous GLP-1 [7–36 amide] is also able to stimulate insulin and inhibit glucagon secretion, thereby altering glucose assimilation. However, with unmodified GLP-1 [7–36 amide], the duration of action is short, and with high doses side effects are common.