Decreased serum adiponectin is associated with dyslipidemia. However, serum adiponectin status has never before been studied in patients with familial-related severe primary hypercholesterolemia (FRSPH). The aim of this study is to measure serum adiponectin level in a group of young patients with FRSPH and determine its correlation with insulin-resistant status. Twenty-three patients with FRSPH [average LDL-cholesterol (LDL-C) = 250.8 (190-610) mg/dL] without clinical manifestations of metabolic syndrome as well as 46 healthy (control) adolescents and young adults (<30 yr old) were included. The serum adiponectin, fasting sugar, insulin, lipids, systolic and diastolic blood pressure (SBP and DBP), and anthropometrical indices such as body mass index and waist circumference were obtained. The homeostasis model assessment (HOMA) was calculated to estimate the insulin resistant status. Compared with healthy controls, patients with FRSPH had a significantly lower mean serum adiponectin level (7.7+/-1.8 microg/mL vs. 10.1+/-4.3 microg/mL, P= 0.013). After adjustment for HOMA and associated covariates, multiple linear regression analysis showed that patients with FRSPH are significantly associated with hypoadiponectinemia. Compared with healthy controls, patients with FRSPH had a significantly lower mean serum adiponectin level (7.7 +/-1.8 microg/mL vs. 10.1+/-4.3 microg/mL, P = 0.013). After adjustment for HOMA and associated covariates, multiple linear regression analysis showed that patients with FRSPH are significantly associated with hypoadiponectinemia. The serum adiponectin levels are lower in young patients with FRSPH without clinical manifestations of metabolic syndrome. The mechanism of hypoadiponectinemia in patients with FRSPH is probably independent of insulin resistance.