The association between insulin and coronary heart disease should be considered within the broader context of the common origins of coronary heart disease and non-insulin dependent diabetes (NIDDM). In this review we summarise findings on the association between circulating non fasting serum insulin levels and major coronary heart disease (CHD) events, during 11.5 years of follow-up in a population-based cohort study of British middle aged men, the British Regional Heart study. Associations between life-style and biological CHD risk factors and the risk of developing NIDDM during 12.8 years of follow-up were also examined in this cohort. A non-linear relation between serum insulin and CHD events was observed, with an almost 2-fold increased relative risk (RR) in the 10th decile of the serum insulin distribution (335.3 mU/L) relative to the 1st to the 9th deciles combined, (age-adjusted RR, 1.9; 95% C.I., 1.6 - 2.4). There was some attenuation of this association on cumulative adjustment for a wide range of biological and life-style CHD risk factors, including HDL-cholesterol, although it remained significant in multivariate analysis. Thus marked hyperinsulinemia predicts CHD events. It is well documented that hyperinsulinemia also antedates clinically diagnosed NIDDM. In this cohort, however, a wide range of additional factors predict both CHD and NIDDM. Obesity and physical inactivity were associated with higher risk and moderate alcohol intake with lower risk of NIDDM (relative to occasional drinkers) in multivariate analysis. Among additional CHD risk factors which antedated NIDDM were Higher blood pressure, raised triglyceride, reduced HDL-cholesterol and raised haematocrit levels. These findings do not suggest a direct atherogenic role for insulin in the development of CHD. We argue that hyperinsulinemia and insulin resistance are markers for common causal factors that link CHD and NIDDM. We highlight the need for a broader concept of the insulin resistance syndrome to accommodate an ever expanding group of risk factors, such as raised haematocrit and microalbuminuria, shared between NIDDM and CHD. There is also a need in future work to focus on factors which influence the development of insulin resistance and on the factors which modulate the progression from insulin resistance to non-insulin dependent diabetes and coronary heart disease. ©1997, Medikal Press.