We examined 125I-insulin-like growth factor I (125I-IGF-I) binding to erythrocytes from 24 normal and 21 non-insulin-dependent diabetic (NIDDM) subjects. 125I-IGF-I binding to human erythrocytes was specifically inhibited by unlabeled IGF-I, and Scatchard analysis indicated a curvilinear plot. There was a significant difference in IGF-I binding between normal and diabetic subjects (7.78 +/- 0.42 vs. 5.80 +/- 0.33%/2.4 x 10(9) cells/ml, P less than 0.001). Among diabetic patients, IGF-I binding to erythrocytes from those with retinopathy and those without retinopathy was comparable. These results suggested that decreased IGF-I binding might be a factor responsible for some pathological features such as delayed wound healing in diabetic patients.