This study was undertaken to ascertain whether patients with insulin resistance syndrome, a cluster of risk factors for coronary artery disease (CAD), are really a high risk population for macro- and microvascular diseases in Japanese NIDDM and borderline glucose-intolerant subjects. A diagnosis of insulin resistance syndrome was made if four of the six following criteria are satisfied: glucose disposal rate < 2.2 mg/kg/min, fasting plasma IRI > 15 μU/ml or peak plasma IRI > 100 μU/ml during meal tolerance test, plasma triglyceride > 150 mg/dl at fasting or > 200 mg/dl after meal, serum HDL-cholesterol < 40 mg/dl, blood pressure > 140 mmHg systolic and > 90 mmHg diastolic or treatment with antihypertensive agents, and body mass index (BMI) > 27 for men or > 25 for women. We compared the prevalence of CAD, cerebral vascular disease (CVD), peripheral vascular disease (PVD), retinopathy and nephropathy between the insulin resistance syndrome group (group A, n = 57) and the remaining group (group B, n = 164). Both groups did not differ with respect to age, duration of diabetes, BMI, fasting plasma glucose, HbA 1c, composition of NIDDM and borderline glucose-intolerance (BGI) or treatment modality. The prevalence of CAD was significantly higher in group A compared with that in group B (31.6% vs. 14.0%, P < 0.002), but not for CVD (8.8% vs. 3.7%, respectively, P = 0.12) or PVD (1.8% vs. 2.4%, respectively, P = 0.76). The prevalence of late-stage retinopathy in group A was significantly higher than that in group B (12.3% vs. 2.4%, respectively, P < 0.005). Macroalbuminuria, but not microalbuminuria, was significantly higher in group A than that in group B (12.3% vs. 3.6%, P < 0.02). We conclude that the insulin resistance syndrome preferentially increases the development of CAD, and is also involved in the progression of microvascular diseases.