The incidence of coronary artery disease (CAD) is markedly increased in both insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM). The background for this coincidence is as yet incompletely understood. In uncomplicated IDDM, the levels of cardiovascular risk factors do not show any substantial abnormalities if the metabolic control is good. However, when diabetic nephropathy ensues, even in its early microalbuminuric stage, blood pressure tends to become elevated and multiple atherogenic plasma lipid abnormalities appear. In juvenile-onset IDDM, increased occurrence of clinically manifest CAD emerges after the age of 30 years and becomes particularly marked in patients with diabetic nephropathy. Premenopausal female patients with IDDM of the same age-a situation in sharp contrast to that in nondiabetics, with a large excess of CAD in men. IDDM may act as a promoter of the progression of atherosclerotic lesions in subjects who are otherwise prone to develop them. This could explain why patients with IDDM have an increased risk of CAD, even in the absence of diabetic nephropathy, which enhances atherogenesis through several mechanisms. NIDDM is associated with multiple changes in cardiovascular risk factors, including abnormalities in the levels and composition of plasma lipids and lipoproteins and increased frequency of hypertension. These changes in cardiovascular risk factors are already present in subjects with impaired glucose tolerance (IGT), the precursor stage of NIDDM. In patients with NIDDM, the incidence of CAD is markedly increased compared to that in nondiabetic subjects of the same age and more markedly in women than in men. Paradoxically, in NIDDM, the frequency of CAD shows very little relationship to the known duration of diabetes. This may be explained by the presence of multiple metabolic and other atherogenic abnormalities in IGT preceding the clinical manifestation of NIDDM. It is even possible that NIDDM and CAD may share common antecedents. The so-called "insulin resistance syndrome" could be such a common antecedent. Although diabetes, in particular NIDDM, is associated with changes in cardiovascular risk factors, the major part of the excess risk of CAD in diabetics is not explained by the effect of diabetes on risk factors, but must be due to an independent effect of diabetes itself or its antecedents through mechanisms that may in part be different in IDDM and NIDDM.