The present study investigates the possible relationship between human β-cell secretory capacity and polymorphism in the 5′-flanking region of the human insulin gene. The glucose potentiation slope was measured in normal and non-insulin-dependent diabetic subjects (NIDDM). This slope, as reported previously (Ward, W. K., et al., Am. J. Physiol. 1984; 246:E405–11), is an index of the ability of hyperglycemia to potentiate the insulin response to arginine and as such is a measure of β-cell responsiveness to glucose. Restriction enzyme analysis using a human insulin gene probe was performed on leukocyte DNA isolated from the same individuals. We conclude that a 1.6 kb polymorphism in the 5′-flanking region of the human insulin gene in both normal and NIDDM subjects has no association with insulin secretory responses as defined here by the glucose potentiation Slope.