Vascular malformations cause discomfort and pain in children and are often as sociated with skeletal hypertrophy. Their molecular basis is poorly understood. Ephrin ligands and Eph receptor tyrosine kinases are involved in embryonic vascu lar development. In mice, some ephrin/Eph family members show a complementary ex pression pattern in blood vessels, with eph- rinB2 being expressed on arterial and EphB4 on venous endothelium. Targeted deletions of the genes reveal their es sential roles for conduit vessel development in mice, suggesting similar functio ns during human vascular development and deregulation in vascular malformations. Here, we have defined the expression patterns of human ephrinB2, EphB4, and Eph B2 in normal vessels of neonates (i.e. umbilici) and adults and compared them wi th those in congenital venous malformations. In adults, normal vessels of the sk in, muscle, and legs express ephrinB2 and EphB2 on arterial endothelial cells (E Cs), whereas EphB4 is found in arteries and veins. In the umbilicus, EphB2 is a specific marker of arterial ECs, whereas ephrinB2 is additionally expressed in v enous ECs, suggesting an arterial function of the veins. In venous malformations , the expression of EphB4 is not altered, but both ephrinB2 and EphB2 are ectopi cally expressed in venous ECs. This may reflect a nonphysiologic arterialization of malformed veins. Our study shows that the arterial markers ephrin B2 and Eph B2 are expressed in a subset of veins, and it remains to be studied whether this is cause or consequence of an altered vascular identity. In mice, some ephrin / Eph family members show a complementary ex pression pattern in blood vessels, with eph-rinB2 being expressed on arterial and EphB4 on venous endothelium. Targeted deletions of the genes reveal their essential roles for conduit vessel development in mice, similar similar events during human vascular development and deregulation in Here, we have defined the expression patterns of human ephrinB2, EphB4, and Eph B2 in normal vessels of neonates (ie umbilici) and adults and compared them wi th those in congenital venous malformations. In adults, normal vessels of the sk in, muscle, and legs express ephrinB2 and EphB2 on arterial endothelial cells (E Cs), while EphB4 is found in arte ries and veins. In the umbilicus, EphB2 is a specific marker of arterial ECs, whereas ephrinB2 is further expressed in v enous ECs, suggesting an arterial function of the veins. In venous malformations, the expression of EphB4 is not altered, but both ephrinB2 This study reflects the nonphysiologic arterialization of malformed veins. Our study shows that the arterial markers ephrin B2 and Eph B2 are expressed in a subset of veins, and it remains to be studied whether this is cause or consequence of an altered vascular identity