question: ABSTRACT We have previously shown increased vascular reactivity to angiotensin (Ang) II in familial combined hyperlipidemia. However, this has not been well studied in familial hypercholesterolemia (FH), a condition with incipient endothelial dysfunction. This study aimed to examine microvascular and macrovascular responses to Ang II in FH. Therefore, we investigated the effects of a 3h infusion of Ang II on blood pressure and forearm skin microvascular function in 16 otherwise healthy FH patients and matched healthy controls. Skin microvascular hyperaemia was studied by laser Doppler fluxmetry during local heating. Microvascular resistance was determined by the ratio mean arterial pressure/microvascular hyperaemia. Macrovascular reactivity was assessed by changes in brachial blood pressure. Compared to the controls, the FH group had increased baseline systolic blood pressure (127±14 vs 115±12 mmHg; P=0.02), while systolic blood pressure responses were similar (+24±9 vs +21±7 mmHg; P=0.26), after 3 h of Ang II infusion. At baseline, there were no group differences in microvascular hyperaemia or resistance. However, after 3 h of Ang II infusion, heat induced microvascular hyperaemia was less pronounced in FH (126±95 vs 184±102 arbitrary units; P=0.01), while microvascular resistance during heat induced hyperaemia was increased (1.9±0.9 vs 0.9±0.8, P=0.01), as compared to controls. Both these responses were further pronounced 1 h after stopping Ang II. In conclusion, despite similar blood pressure responses to Ang II in FH and controls, microvascular dilatation capacity was impaired in FH, indicating endothelial dysfunction. These findings and increased microvascular resistance may lead to hypertension and microvascular complications in FH.