B7-1 expression, Induced by transfectlon in poorly Immunogenic murine tumours, was shown to elicit a T cell-mediated rejection of these tumours and further active immunity against the nontransfected tumour. We therefore asked to what level similarly induced expression of B7 on human melanoma cells would affect the antigen-dependent responses of tumour-speclflc T cell clones In vitro. Data presented show that B7-1 expression by melanoma lines: (I) significantly Induced, or improved, an IL-2-dependent prollferatlve response of such clones to the antigen; (II) Increased the amount of IL-2 produced by two clones In response to the parental non-transfected tumour cells; and (ill) increased the TNF responses of all the CD4 + clones. However, despite these clear co-stimulatory effects on antigen-Induced responses of all T cell clones, which demonstrated an effective interaction of the B7-1 transfected molecule with one or the other of Its counter-receptors expressed on T cell clones, B7 co-stimulation did not correct the defect of IL-2 secretion exhibited by many of these clones in response to In vitro antigen presentation by melanoma cells. We further show that defective IL-2 secretion in response to melanoma antigens was not due to a T cell clone refractoriness induced by the culture, since one of these clones could be Induced to secrete IL-2 by an antigen-expressing melanoma line, upon increased lymphocyte function associated antlgen-3 expression Induced by gene transfectlon. Together these data suggest that defective IL-2 secretion by many tumour-infiltrating lymphocytes clones in response to antigen presentation by melanoma cells In vitro is not exclusively due to the inability of these cells to provide an appropriate co-stimulation through the B7-1 molecule.