In familial hypercholesterolemia (FH) elevated Lp(a) concentrations are more frequent than in the general Caucasian population, but the clinical relevance of Lp(a) as a risk-factor in this group of patients is controversial. In 91 adult patients with heterozygous FH due to LDL-receptor defect we analyzed the correlation between Lp(a) concentrations, presence of coronary heart disease (CHD) and degree of atherosclerosis of the carotid arteries assessed by duplex scan. Coronary heart disease was present in 32 patients (24 males, 8 females). In the group without CHD the median of the Lp(a) distribution was 23 mg/dl, in the group with CHD 43 mg/dl (P < 0.05). The median of Lp(a) was 8 mg/dl in patients without pathological changes in the duplex scan of the carotids, 13 mg/dl in the group with intimal thickening, 25 mg/dl in patients with non-obstructing plaques, and 45 mg/dl in presence of > 30% luminal obstruction (P < 0.01). The role of Lp(a) as an independent risk factor was analyzed by stepwise logistic regression together with age, sex, LDL-, HDL-cholesterol, serum triglycerides, smoking status and presence of hypertension. For the prediction of CHD only age, HDL cholesterol and gender reached statistical significance. Lp(a) was, however, the lipoprotein parameter with the highest discriminative strength for the presence of a pathological duplex scan (P = 0.016), followed by LDL- (P = 0.03), and HDL-cholesterol (P = 0.03). These results provide direct evidence for a close correlation between Lp(a) and the rate of progression of atherosclerosis in FH, already at early, asymtomatic stages.