The high-density lipoprotein (HDL) subclass distribution was examined by gradient gel electrophoresis (gge) in 154 human cord blood samples, and determinations of triglyceride, total cholesterol, and HDL-cholesterol levels were performed. Three distinct gge patterns were recognizable. The first pattern, termed the normal (gge) pattern, was distinguished by a prominent double peak in the (HDL2a)ggeregion and a pronounced peak in the (HDL3b)ggeregion. Minor peaks, or shoulders, were also seen in the (HDL2b)ggeand (HDL3C)ggeregions, and a valley was present in the (HDL3a)ggeregion. This pattern was associated with normal lipid levels for cord blood plasma (mean triglycerides: 30-42 mg/dl; mean total cholesterol 62-85 mg/dl; mean HDL-cholesterol: 34-41 mg/ dl).The second pattern, termed the 2b(gge) pattern, contained a major peak in the (HDL2b)ggeregion rather than the shoulder seen in the normal (gge) pattern, while the (HDL2a)gge, (HDL3b)gge, and (HDL3c)ggeregions were less pronounced. This pattern was associated with elevated total cholesterol and HDL-C levels (means 85-102 and 49-56 mg/dl, respectively). The third pattern, termed the 3b(gge) pattern, was characterized by a paucity of material in the (HDL2b)ggeregion, a single peak in the (HDL2a)ggeregion, and either a relative increase in the (HDL3b)gge region, or a simultaneous increase in both (HDL3b)ggeand (HDL3c)gge. This pattern was associated with elevated triglyceride levels (means 78-88 mg/dl) and decreased HDL-C levels (means 20-30 mg/dl). Only two infants had a simultaneous elevation of triglycerides and total cholesterol and both cases exhibited the 3b(gge) pattern. Our study demonstrates that although the triglyceride and cholesterol levels in the newborn are much lower than those in adults, they are the important factors associated with the HDL subclass distribution. Elevated cholesterol was related to increased particles in the (HDL2b)ggeregion while elevated triglyceride levels were associated with a decrease in (HDL2b+2a)ggeparticles and a concomitant increase in (HDL3b)ggeparticles.