Patients with familial hypercholesterolemia (FH) are especially at risk for premature cardiovascular disease (CVD). Recent studies revealed C-reactive protein (CRP) as a strong predictor of future first or recurrent CVD events, suggesting that CRP plays an important role in the development of atherosclerosis. The aim of this study was to evaluate the effect of one year of simvastatin treatment on serum levels of CRP and to assess the influence of risk factors for CVD on CRP concentrations in patients with FH. We measured baseline CRP levels in 337 patients with FH. A second blood sample, collected after one year of treatment with simvastatin (20--40 mg once daily) was measured in a subgroup of 129 patients. Patients with CVD present at baseline had significantly higher serum levels of CRP (2.26 mg/l versus 1.55 mg/l, P<0.001). CRP levels were associated with smoking, body mass index, age, levels of triglycerides (TG), and the use of NSAIDs or anticoagulation drugs. Simvastatin therapy significantly improved lipid profiles in the intervention group. There was a small, but non-significant decrease of CRP levels upon treatment. CRP decreased from 1.51 mg/l median (interquartile range (IQR) 0.76--3.41) at baseline to 1.24 mg/l median (IQR 0.72--2.92) after treatment, (P=0.328). In conclusion, CRP levels were associated with the presence of CVD in FH patients. Simvastatin therapy had no significant effect on CRP levels in these patients.