We have examined the risk of subsequent ischemic heart disease (IHD) in men according to their initial fasting plasma glucose level in a prospective cohort study (Caerphilly Collaborative Study) of 4860 middle aged men from South Wales and Bristol, U.K. Ninety-four men reported themselves to be diabetic at initial screening and fasting venous plasma glucose levels were determined in these men and in a further 4519 non-diabetic men. At follow-up new IHD events occurred twice as commonly in diabetics compared to non-diabetics and overall mortality was increased 4-fold. Among non-diabetics however, increased IHD events only occurred in men with fasting values at the upper end of the distribution of baseline plasma glucose values [at 6.8 mmol/l (122 mg/dl) or more]. This association was reduced, but remained statistically significant, after adjusting for factors associated with plasma glucose levels; body mass index, plasma triglyceride, smoking habit and pre-existing IHD. In conclusion there is no evidence of a consistent, graded increase in risk of IHD by initial fasting plasma glucose level although the risk is significantly increased in men with baseline plasma values at 6.8 mmol/l (122 mg/dl) or more, and also in diabetics. This study suggests that such levels probably represent a pre-diabetic state in many individuals. Appropriate non-pharmacological intervention may be useful in halting the progression to the diabetic state, although this should be tested in experimental studies.