Iodine-123-MIBG has been introduced as a biochemical marker in assessing pulmonary endothelial cell integrity and myocardial P-adrenergic sympathetic innervation, The aim of this study was to evaluate I-123-MIBG lung uptake in diabetic patients with and without coronary artery disease. Methods: Forty-four nonsmoking patients with normal respiratory function tests were included: 12 diabetics, 11 diabetics with coronary artery disease, 14 nondiabetic patients with coronary artery disease and 7 age-matched controls were imaged with I-123-MIBG and (TI)-T-201 scintigraphy. The lung retention of I-123-MIBG, cardiac sympathetic innervation (heart-to-upper mediastinum ratio of I-123-MIBG) and (TI)-T-201 lung-to-heart ratio were determined in all cases, Results: In diabetics with coronary artery disease, significantly prolonged lung retention and decreased cardiac uptake of I-123-MIBG were found. The lung retention of I-123-MIBG was inversely correlated with the heart-to-upper mediastinum ratio in this group. Lung-to-heart ratios of (TI)-T-201 were significantly increased in patients with coronary artery disease but there was no significant difference between diabetics and nondiabetics, Conclusion: Prolonged lung retention of I-123-MIBG was associated with decreased cardiac sympathetic innervation in diabetic coronary artery disease patients. It seems that passive pulmonary congestion or cardiac dysfunction itself did not influence I-123-MIBG lung uptake. Increased lung extraction of I-123-MIBG is highly suggestive of ongoing pulmonary endothelial dysfunction together with ischemic events in diabetics.