In this very preliminary analysis of a small sample of subjects with hypercholesterolemia, we found that genetic variation in NPC1L1, as defined by a three-site SNP haplotype, was significantly associated with inter-individual variation in the response of plasma LDL cholesterol to 12 weeks of treatment with ezetimibe 10 mg daily. Here, NPC1L1 is linked to familial hypercholesterolemia.