This study investigated whether the presence of coronary artery disease (CAD) in patients with a low conventional coronary risk profile is associated with perturbations of free fatty acid (FFA) metabolism. All patients studied were non-smokers, normoglycemic, normotensive, nonobese, and had triglycerides, low-density lipoprotein and high-density lipoprotein (HDL) cholesterol in the reference ranges. An FFA tolerance test was designed, consisting of a heparin injection 4h after an oral fat load which induced a marked increase in plasma FFA concentrations. Measurements were made before the fat load, after 4 h (immediately before heparin injection), and after 4.5, 8, and 10 h. The test was carried out in 28 male CAD patients and in 25 male controls free of CAD as verified by coronary angiography. In the fasting state the two groups showed no differences in conventional risk factors with the exception of HDL cholesterol (patients 0.97 +/- 0.04 mmol/l, controls 1.13 +/- 0.05 mmol/l, P = 0.013). During the test the best discriminator found was FFA at 8 h (P = 0.0009) and, very pronounced, at 10 h (P = 0.000). We conclude that perturbed FFA metabolism in an FFA tolerance test can indicate the presence of CAD in men with a low conventional coronary risk profile, possibly as an early indicator of the metabolic syndrome.