Interrelationships of high-density lipoprotein cholesterol (C-HDL) with total plasma cholesterol (TC), triglyceride, and low-density lipoprotein cholesterol, as well as longitudinal maintenance of C-HDL rank order (tracking) from birth to age 2 years were assessed in 76 hypercholesterolemic neonates (cord blood, TC > 95 mg/dl) with focus upon 34 hyperalphalipoproteinemic neonates who had cord blood C-HDL > 61 mg/dl, ≥ the 99th percentile. Cord blood C-HDL correlated closely (P< 0.01) with C-HDL at 6, 12, and 18 to 24 months (r= 0.32, 0.49, and 0.39, respectively). C-HDL levels at 12 months and 18 to 24 months were closely associated (r= 0.68 andP< 0.01). C-HDL at birth, 6, and 12 months correlated positively (P< 0.01) with TC levels (r= 0.28, 0.30, and 0.36, respectively). Conversely, C-HDL at birth, 6 and 12 months correlated inversely with TG (P< 0.01) (r= −0.41, −0.40, and −0.49, respectively). At birth and at 18 to 24 months, C-HDL correlated inversely (p< 0.05) with C-LDL (r= −0.36 and —0.31, respectively). Of neonates having cord blood C-HDL in the highest quartile, 38, 56, and 60%, respectively at ages 6, 12, and 18 to 24 months retained C-HDL levels in the highest quartile; 56, 75, and 70%, respectively, retained C-HDL levels > the 50th percentile. Of 13 neonates having the highest initial cord blood C-HDL levels, cord blood C-HDL ≥ 69 mg/dl, nine had one or more C-HDL values > 70 mg/dl (the 90th percentile for childhood), throughout the 12− to 60-month follow-up period. Moreover, where more than one follow-up measurement was available, there was relative stability of elevated C-HDL measurements. Many infants with cord blood hyperalphalipoproteinemia are likely to have persistent elevations of C-HDL at ages 1 and 2 years. If they maintain elevated C-HDL into adulthood, they may, speculatively, be at reduced risk for coronary heart disease, given the strong inverse association of C-HDL with coronary heart disease.SpeculationMany infants with cord blood hyperalphalipoproteinemia are likely to have persistent elevations of high-density lipoprotein cholesterol (C-HDL) at ages 1 and 2 years. If they maintain elevated C-HDL into adulthood, they may, speculatively, be at reduced risk for coronary heart disease, given the strong inverse association of C-HDL with coronary heart disease.