Certain leukocyte subpopulations may be of particular importance in atherosclerosis. By flow cytometry, we analyzed leukocyte subpopulations in familial hypercholesterolemia (FH) and healthy children. FH children with low HDL-C had a shift in the monocyte subpopulations towards a pro-inflammatory phenotype. Monocytes expressing CD18 and serum E-selectin were also higher in FH children with low HDL-C. Our data suggest an activation of monocytes at a very early stage of atherosclerosis in humans.