Umbilical plasma levels of lipoproteins-cholesterol were measured in 60 premature (less than 37 weeks), 60 small for gestational age (SGA, greater than 37 weeks), and 60 full term newborns (greater than 37 weeks) to ascertain the relationship between gestational age, infant's weight and concentration of plasma lipoprotein cholesterol. Umbilical levels of total cholesterol (TC), unesterified cholesterol (UC), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) in premature newborns were significantly higher (P less than .001) than in term infants. The levels of TC, UC, HDL-C and very low density lipoprotein cholesterol (VLDL-C) were substantially higher (P less than .05) in umbilical cord plasma of SGA newborns than in cord plasma of full term newborns. Lecithin:cholesterol acyltransferase activity in cord plasma was indirectly assessed by measuring the ratio of esterified cholesterol to unesterified cholesterol (CE/UC). This ratio was significantly lower (P less than .01) in preterm and SGA than in full term newborns. In addition, plasma TC, UC, LDL-C and HDL-C levels were inversely correlated with gestational age of newborns. By contrast, CE/UC ratio had an inverse correlation with gestational age and HDL-C of the newborns. These findings suggest that the levels of TC in newborns are regulated by the uptake of LDL-C by the fetal adrenal and, additionally, by the lecithin:cholesterol acyltransferase (LCAT) activity of newborn plasma. Only by careful follow-up of hyperlipidemic neonates can the true incidence of familial hyperlipoproteinemia and the value of early diagnosis be assessed.