We assessed plasma lipid levels in children and adolescents who were on various drug regimens and who were attending a specialized lipid treatment center. All subjects had familial hypercholesterolemia (FH), and the study group included 30 subjects with heterozygous (He) and three with homozygous (Ho) FH. In the 30 He FH subjects treated with 5 to 30 g/day of a bile-acid-binding resin, plasma lipid levels were still substantially above optimal (less than or equal to 50th percentile for age and sex), although statistically significant (p less than 0.001) reductions in total and low density lipoprotein (LDL) cholesterol of 15% and 21% compared with baseline were achieved. In eight subjects who received resin plus niacin, additional reductions in total and LDL cholesterol of 15% and 17%, respectively, were achieved. Even though the combination therapy produced reductions in total, LDL, and LDL/high density lipoprotein cholesterol of 29%, 37%, and 47%, respectively, compared with baseline, resulting absolute levels were still well above optimal. Six subjects with severe He FH received a 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor (lovastatin, 80 mg/day or simvastatin, 40 mg/day), and substantial total and LDL cholesterol reductions on the order of 35% and 41%, respectively, were found compared with diet alone. The decreases were substantially greater than those achieved with either resin or resin plus niacin. In a number of these subjects, absolute lipid levels were approaching optimal levels. In the three Ho FH subjects, the response to HMG CoA reductase inhibitors was variable but generally poor.(ABSTRACT TRUNCATED AT 250 WORDS)