To examine whether the decrease in fasting and postprandial beta-cell responsiveness (M) increases with the duration of diabetes, a meal-tolerance test was conducted in 1466 type 2 diabetics and fasting (Mo) and 2 h postprandial (M1) beta-cell responsiveness was calculated. Fasting C-peptide, postprandial C-peptide, M0 and M1 were lower, and HbA1c values higher in patients with diabetes duration > 10 years. After adjustment for age, sex and body mass index, diabetes duration was negatively correlated with fasting C-peptide (gamma = -0.102), postprandial C-peptide (gamma = -0.356), Mo (gamma = -0.263) and M1 (gamma = -0.315; P<0.01 respectively); HbA1c was negatively correlated with postprandial C-peptide (gamma = - 0.264), Mo (gamma = - 0.379) and M1 (gamma = - 0.522), but positively correlated with fasting C-peptide (gamma = 0.105; P<0.01 respectively). Multiple regression analysis revealed Mo, M1 and homeostasis assessment for insulin resistance to be independent predictors of HbA1c. Thus, both fasting and postprandial beta-cell responsiveness decrease with the duration of diabetes, with postprandial beta-cell responsiveness likely to be a more important relative determinant for glycemic control than fasting beta-cell responsiveness.