In order to determine whether low levels of high-density lipoprotein cholesterol (HDL-C), which are predictive of ischemic heart disease in the general population, can also predict death from ischemic heart disease among diabetic men, we contrasted lipoprotein and other heart disease risk factors in 62 men with non-insulin-dependent diabetes mellitus, 14 of whom died of ischemic heart disease during a 12-year follow-up period. Compared to all other diabetic men, those who died of ischemic heart disease were older, had higher levels of fasting plasma glucose (FPG) total plasma cholesterol, and triglycerides, lower HDL-C levels, and higher low-density lipoprotein cholesterol (LDL-C) levels and were more likely to have been cigarette smokers; only total cholesterol, LDL-C, and the LDL/HDL ratio were statistically significant. Age, FPG, total plasma cholesterol, and LDL-C were all independently predictive of fatal heart disease by multivariate analysis. Neither HDL-C nor the LDL/HDL ratio predicted ischemic heart disease death better than the total plasma cholesterol or LDL-C. The use of HDL-C, LDL-C, or total plasma cholesterol level in the model did not eliminate the significant association with FPG, which suggests that the noxious effect of hyperglycemia is independent of the changes in blood lipids.