The authors measured the relation between C-reactive protein, alpha 1 acid glycoprotein and albumin, an acute phase protein, and subsequent risk of myocardial infarction and coronary heart disease death in a nested case-control study among the Multiple Risk Factor Intervention Trial (MRFIT) participants. There were 98 myocardial infarction cases, 148 coronary heart disease deaths, and 491 controls. The cases and controls were followed for up to 17 years for deaths and 6-7 years for myocardial infarction cases and controls. There was a significant association between available distribution of C-reactive protein and subsequent coronary heart disease mortality. For smokers at baseline, the risk of coronary heart disease deaths in quartile 4 of C-reactive protein as compared with quartile 1 was 4.3 (95% confidence interval 1.74-10.8). The association persisted when adjusted for characteristics related to smoking and smoking cessation during the trial and to pulmonary function. There was no relation between alpha 1 acid glycoprotein and either myocardial infarction or coronary heart disease death. Albumin was inversely related to coronary heart disease death only for deaths that occurred between 7 and 13 years after baseline, consistent with previous MRFIT analyses. This is the first prospective study in "healthy but high risk individuals" to document the relation between C-reactive protein and coronary heart disease mortality.