Macrosomia is associated with alterations in lipoprotein composition and concentration at birth. Exposure to diabetes in utero has been established as a significant risk factor for some of the components of metabolic syndrome. The aim of this study was to investigate the effect of macrosomia on lipid metabolism, aortic intima-media thickness (aIMT) and subsequent atherogenic risk in newborn infants. Aortic intima-media thickness was measured in 40 macrosomic neonates of diabetic mothers (group A), 30 macrosomic neonates of healthy mothers (group B) and 30 healthy neonates (group C). Lipid profile was determined in all infants and their mothers. Mean aIMT was significantly higher in macrosomic neonates of diabetic and healthy mothers (0.56 +/- 0.06 and 0.49 +/- 0.03 mm respectively) than in controls (0.39 +/- 0.03 mm). Weight-adjusted aIMT in macrosomic neonates of diabetic mothers (0.129 +/- 0.013 mm/kg) was significantly higher than in groups B and C (0.114 +/- 0.008 and 0.113 +/- 0.011 mm/kg respectively). There were significant alterations of total serum, high-density lipoprotein (HDL), very low-density lipoprotein (VLDL) cholesterols and triglyceride levels in the macrosomic neonates of diabetic mothers compared with controls. Macrosomia was associated with increased lipid concentrations. Macrosomic neonates of diabetic mothers have significantly higher aIMT with lipid alterations. This may play a role in the pathogenesis of atherosclerosis in adult life.