Background and Design: Immunohistochemical analysis using four monoclonal antibodies specific for endo thelium was performed to evaluate the possible role the endothelium may play in the pathogenesis of port-wine stains. In 11 patients with port-wine stains, biopsy specimens were obtained from involved and normal skin. On frozen tissue sections,we studied and compared the distribution and staining pattern of PAL-E, anti-intercellular adhesion molecule-1 (ICAM-1), anti-endothelial leukocyte adhesion molecule-1 (ELAM-1), and anti-factor VIIIrAg (FVIIIrAg), all recognizing specific epitopes of vascular endothelial cells. Results: The PAL-E, anti-FVIIIrAg, and anti-ICAM-1 antibodies showed a similar distribution and staining pattern. The intensity of staining was equally strong with PAL-E and FVIIIrAg, while the expression of ICAM-1 was moderate. The ELAM-1 antibody exhibited only a weak expression in about 70% of evaluated specimens. No substantial differences in the intensity and distribution pattern of expression of these proteins could be demonstrated between normal skin and port-wine stains. Conclusion: Our findings suggest that the abnormal vessel pathologic findings in port-wine stains are not due to defects associated with the endothelium. According to PAL-E antibody staining properties, port-wine stain vessels could be classified as capillaries and/or postcapillary venules and small veins.