Apolipoprotein A-l (Apo A-l) is the major protein constituent of high-density lipoprotein (HDL) and Apo A-l plays an important role in lipid metabolism and may be protective against atherosclerosis in adults. However, little is known about HDL and Apo A-l in the developing human fetus. Herein we investigated the relationship of Apo A-l levels in umbilical cord blood at delivery to gestational age and HDL cholesterol. Fetal plasma levels of Apo A-l, which were not correlated with those in maternal plasma, were significantly lower among newborns delivered at 21-26 wk gestation (52 ± 4.4 tag/ dl, mean ± SE) than in those delivered at 33-34 wk gestation (87 ± 5.8 mg/dl). Thereafter, the mean umbilical cord plasma levels of Apo A-l remained relatively constant (101 mg/dl at 39-40 wk of gestation). We found no significant correlations between Apo A-l levels and fetal sex, race, or delivery method. At equivalent gestational ages and birth weights, however, Apo A-l levels in white newborns tended to be lower than those in black infants. The Apo A-l/HDL cholesterol ratio in umbilical cord blood rose progressively from 2.5 (27-28 wk gestation) to 3.8 at term, due largely to increased Apo A-l levels but little change in the mean HDL cholesterol levels, which ranged from 22-24 mg/dl at each gestational period. These results are suggestive that fetal plasma Apo A-l is derived solely from fetal sources and that the rate of production and/or clearance of Apo A-l is altered during the latter third of human intrauterine development. © 1988 International Pediatric Research Foundation. Inc.