The Leu7Pro gene variant of the signal peptide part of neuropeptide Y (NPY), has been shown to affect cholesterol metabolism in obese adults. This study investigates whether the Leu7Pro polymorphism in the prepro-NPY has an impact on serum lipid concentrations in preschool-aged children at 5 and 7 yr of age. As birth weight may influence future lipid values, we also investigated whether Leu7Pro polymorphism is associated with birth weight. The study comprised 688 children participating in the Special Turku Coronary Risk Factor Intervention Project. Fasting lipid concentrations were determined first at the age of 5 yr and again at the age of 7 yr. The Leu7Pro polymorphism was not associated with serum total or low density lipoprotein cholesterol values in boys or in girls. However, Pro7 substitution in prepro-NPY was constantly associated with 14-17% higher mean serum triglyceride values in the boys at the ages of 5 and 7 yr (P = 0.023). In addition, boys with the Pro7 substitution had, on the average, a 193-g higher birth weight than boys homozygous for Leu7 (P = 0.03). The Leu7Pro polymorphism may thus be linked with serum triglyceride concentrations, but not with serum cholesterol concentrations, in gender-specific manner in preschoolers.