Rhinoviruses, which cause common colds, possess over 100 serotypes, 90% of which (the major group) share a single receptor. Lymphocyte function associated molecule 1 (LFA-1) mediates leukocyte adhesion to a wide variety of cell types by binding to intercellular adhesion molecule 1 (ICAM-1). We demonstrate identity between the receptor for the major group of rhinoviruses and ICAM-1. A major group rhinovirus binds specifically to purified ICAM-and to ICAM-expressed on transfected COS cells, and binding is blocked by three ICAM-monoclonal antibodies (MAb) that block ICAM-i-LFA-1 interaction, but not by an ICAM-MAb that does not block ICAM-1-LFA-1 interaction. This suggests that the ICAM-contact site (s) for LFA-1 and rhinoviruses is proximal or identical. In addition, KAY-1 YAb block the cytopathic effect in HeLa cells mediated by representative major but not minor group rhinoviruses. ICAM-is induced by soluble mediators of inflammation, suggesting that the host immune response to rhinovlrus may facilitate spread to uninfected cells.