In the accompanying manuscript (p. 405) we describe the up-regulation of the adhesion molecules LFA-3 and ICAM-1 on the surface of cytomegalovirus (CMV)-infected fibroblasts from days 1 to 5 post-infection. Peak expression was seen on day 2, when LFA-3 was twice, and ICAM-1 three times, the level on uninfected fibroblasts. The present study demonstrates a parallel increase in the adhesion of peripheral blood leucocytes to the CMV-infected fibroblasts, which was significantly greater than adhesion to uninfected fibroblasts from days 2 to 4 post-infection. This effect was seen from 2 to 24 hr of leucocyte-fibroblast co-culture. The increased binding to infected fibroblasts was accounted for by the CD2+ subset of lymphocytes. All subpopulations of CD2+ lymphocytes, namely CD3+, CD4+, and CD8+ cells, demonstrated increased adhesion to CMV-infected fibroblasts, suggesting that the CD2-LFA-3 interaction was an important component of the increased binding. This proposal was supported by the fact that the pretreatment of infected fibroblasts with monoclonal antibodies specific for LFA-3, significantly blocked the binding of CD2+ lymphocytes. Supernatants from infected fibroblasts, or co-cultures of leucocytes and infected fibroblasts, could transfer increased leucocyte binding to uninfected fibroblasts, suggesting that CMV might accentuate inflammatory responses. As lymphocytes can be activated by the CD2 pathway, CMV might also provoke nonspecific leucocyte responses to uninfected as well as infected cells, which could possibly contribute to tissue damage.