Intercellular adhesion molecule-1 (ICAM-1)/LFA-1-mediated cell-cell adhesion is essential for various immunologic functions. It was previously shown that some of these, including non-MHC-restricted cytotoxicity, could be inhibited by soluble forms of ICAM-1. Here, we characterize the effects of soluble ICAM-1 on MHC-restricted specific T cell/melanoma interactions. Tumor-infiltrating lymphocyte (TIL) clones, as well as melanoma lines from the same tumor specimens, were established. The TIL clones used were able to form conjugates with the autologous tumor and to kill it in an MHC-restricted way. TIL/melanoma interaction also induced increased cytokine production in TIL. Using this system, we could demonstrate that purified soluble ICAM-1 (950 ng/ml) or 12-fold concentrated cell-free melanoma supernatants, containing shed ICAM-1 (1000 ng/ml), were able to inhibit conjugate formation between T cell clones and the autologous melanoma cells as efficiently as mAb against CD11a. In addition, free ICAM-1 abrogated the MHC-restricted killing of the melanoma exerted by T cell clones and blocked the induction of cytokines in T cells due to the contact with autologous tumor cells.