While a certain degree of structural and functional intra‐lobular heterogeneity of sinusoidal endothelial cells has been observed in rodents, little information is available about the zonal characteristics of sinusoidal endothelial cells in the human liver acinus. We have therefore examined the intra‐acinar distribution of a panel of endothelial markers in the normal human liver, including: (a) structural markers of continuous and sinusoidal endothelia (PECAM‐1, CD‐34 protein, VE‐cadherin, 1F10 antigen), (b) functional markers specific for sinusoidal endothelial cells, as previously determined in the laboratory (CD4 protein, the lipo‐polysaccharide‐binding protein receptor (CD 14), aminopeptidase N, ICAM‐1, receptors II and III for the Fc fragment of immunoglobulins G), (c) endothelial cell‐matrix adhesion proteins and leukocyte‐endothelial cell adhesion molecules. We observed a heterogeneous distribution for: (a) the 1F10 antigen, whose distribution in the human liver acinus was restricted to vessels situated along the axis of acinar zone 1, (b) the lipopolysaccharide‐binding protein receptor and the receptor III for the Fc fragment of IgG, not expressed or only barely expressed in acinar zone 1. The distribution of the other markers tested did not display significant intra‐lobular variation. Our in situ results suggest the existence of a degree of zonal heterogeneity in the structural and functional characteristics of sinusoidal endothelial cells in the human liver acinus. This might contribute to the constitution of distinct microenvironments within the human liver parenchyma.