CONTEXT: The insulin response to meal ingestion is more rapid in the morning than in the afternoon. Whether this is explained by a corresponding variation in the incretin hormones is not known. OBJECTIVE: Our objective was to assess islet and incretin hormones after meal ingestion in the morning vs. afternoon. DESIGN, SETTINGS, AND PARTICIPANTS: Ingestion at 0800 and 1700 h of a standardized meal (524 kcal) in healthy lean males (n = 12) at a University Clinical Research Unit. MAIN OUTCOME MEASURES: We assessed early (30-min) area under the curve (AUC30) of plasma levels of insulin and intact (i) and total (t) glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) after meal ingestion and made an estimation of beta-cell function by model analysis of glucose and C-peptide. RESULTS: Peak glucose was lower in the morning than in the afternoon (6.1 +/- 0.2 vs. 7.4 +/- 0.3 mmol/liter, P = 0.001). AUC30(insulin) (4.9 +/- 0.6 vs. 2.8 +/- 0.4 nmol/liter . 30 min; P = 0.012), AUC30(tGLP-1) (300 +/- 40 vs. 160 +/- 30 pmol/liter . 30 min, P = 0.002), AUC30(iGIP) (0.7 +/- 0.1 vs. 0.3 +/- 0.1 nmol/liter . 30 min, P = 0.002), and AUC30(tGIP) (1.1 +/- 0.1 vs. 0.6 +/- 0.1 nmol/liter . min, P = 0.007) were all higher in the morning. AUC30(iGLP-1) (r = 0.68; P = 0.021) and AUC30(iGIP) (r = 0.78; P = 0.001) both correlated to AUC30(insulin). Model analysis of beta-cell function showed a higher first-hour potentiation factor in the morning (P = 0.009). This correlated negatively with the 60-min glucose level (r = -0.63; P < 0.001). CONCLUSIONS: The early release of GLP-1 and GIP are more pronounced in the morning than in the afternoon. This may contribute to the more rapid early insulin response, more pronounced potentiation of beta-cell function, and lower glucose after the morning meal.