Tumor clones isolated from the same subcutaneous metastatic lesion of a melanoma patient were used to investigate the potential role of beta 1-integrins (VLA) in the lysability of neoplastic cells by autologous CD3+, WT31+, CD8+ cytotoxic T-cell clones. Phenotypic analysis of melanoma clones for expression of VLA molecules revealed a subset of clones with high expression of VLA-2, VLA-5, and VLA-6. This subset was also characterized by increased susceptibility to lysis by tumor-specific and nonspecific cytotoxic T-lymphocytes from either TILs or PBLs. Blocking assays with monoclonal antibodies indicated that anti-VLA-2, -5, and -6 antibodies could significantly reduce the lysis of VLA-2+, VLA-5+, and VLA-6+ melanoma clones by either specific and nonspecific CTLs. By contrast, no inhibition was seen on lysis of VLA-2-, VLA-5-, and VLA-6-negative tumor cells. These data indicate that expression of some beta 1-integrins on human melanoma can influence the specific and nonspecific T-cell-mediated recognition of neoplastic cells.