Background: African Americans have a greater insulin response after glucose challenge than do European Americans. Factors underlying this response are unknown. Objective: We determined the insulin, C-peptide, and incretin responses to a mixed macronutrient meal in African American and European American children. We hypothesized that 1) African Americans would have greater postprandial insulin and C-peptide responses, 2) African Americans would have higher incretin responses, and 3) the greater β cell response among African Americans would be explained by greater incretin responses. Design: Subjects were 34 African American and 18 European American children. Glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) were measured after the subjects consumed a liquid mixed meal. Insulin, C-peptide, and incretin responses were derived from the area under the curve (AUC) for minutes 0-30 (early response) and minutes 30-180 (late response) after meal ingestion. Results: The early insulin response was higher in African American (14 565 ± 6840 pmol/L x 30 min) than in European American (7450 ± 4077 pmol/L x 30 min; P < 0.01) children. Early C-peptide AUC did not differ by ethnicity (African Americans: 34.8 ± 12.5; European Americans: 28.6 ± 12.5 nmol/L x 30 min; P = 0.10). Early and late GLP-1 responses were lower in African Americans than in European Americans: 108.1 ± 56.4 compared with 160.5 ± 90.8 pmol/L x 30 min and 509.4 ± 286.9 compared with 781.9 ± 483.4 pmol/L x 150 min, respectively (P < 0.05 for both). The GIP response did not differ between groups. Conclusions: The greater early insulin response in African Americans than in European Americans is not due to differences in circulating GLP-1 or GIP and may be due to lesser insulin clearance. Further research is needed to determine the physiologic implications of lower GLP-1 among African Americans. © 2008 American Society for Nutrition.