Microsomal triglyceride transfer protein (MTP) is a lipid transfer protein that is required for the assembly and secretion of very low density lipoproteins (VLDL) by the liver and chylomicrons by the intestine. The common G-493T polymorphism of the MTP promoter has been shown to be associated with decreased plasma LDL-cholesterol and ApoB content of VLDL. The purpose of the present study was, therefore, to investigate the association of this mutation with variations in lipid and apoprotein levels, lipoprotein subclass profiles and coronary heart disease (CHD) risk in a population-based sample of 1226 male and 1284 female Framingham Offspring participants. In men and women, no significant association was found between the G-493T MTP polymorphism and variations of plasma levels of total cholesterol, LDL-cholesterol, apoprotein B, HDL-cholesterol, apoprotein AI and triglycerides. In order to further investigate potential relationships with variations of lipoprotein phenotypes, lipoprotein subclass profiles were measured using automated nuclear magnetic resonance (NMR) spectroscopy. Each NMR profile yielded information on lipid mass of VLDL, LDL, and HDL subclasses. In both genders, there was no significant association between the G-493T polymorphism and variability of lipoprotein subclass distributions or lipoprotein particle size. Furthermore, no significant association was found between the polymorphism of the MTP promoter and prevalence or the age of onset of CHD. Thus, our results suggest that the G-493T mutation in the MTP promoter is unlikely to have significant implications for cardiovascular disease in men and women.