The expression of intercellular adhesion molecule 1 (ICAM-1) by endothelial cells is important for the regulation of adhesion and transendothelial migration of a variety of leukocytes that express the integrins lymphocyte functionassociated antigen 1 (LFA-1) and/or Mac-1. Here, we demonstrate strain-specific differences in the ability of measles virus (MV) to induce ICAM-1 expression. The vaccine strain Moraten (Mor) rapidly induced high levels of ICAM-1 mRNA and protein expression, whereas the vaccine strain CAM-70 and the Edmonston wild type (Edwt) strain were far less effective, even when they were used at very high multiplicities of infection (MOIs). Strain-specific differences in the induction were not a consequence of differences in the ability to infect ECs. Furthermore, induction of ICAM-1 by Mor was not dependent on de novo expression of MV or cellular proteins. Dual-immunofluorescence analysis indicated that there was no association between the expression of either MV nucleocapsid or hemagglutinin protein and the induction of ICAM-1 expression. Some human umbilical vein endothelial cells (HUVECs) that expressed high nucleocapsid protein in response to either Mor or CAM-70 failed to express elevated ICAM-1, whereas some HUVECs that were incubated with Mor expressed high ICAM-1 prior to expression of MV nucleocapsid protein. Strain-specific differences in the ability of Mor and CAM-70 to induce ICAM-1 correlated with their ability to activate the latent transcription factor NF-B. These studies suggest a preexisting component of MV particles that leads to strain-specific differences in the activation of NF-B and the induction of ICAM-1 gene expression.