Cytotoxic T lymphocytes (CTL) are equipped with a range of effector functions that contribute both to the control of intracellular pathogens and dysregulated cellular proliferation and to the development of certain immunopathologies such as autoimmune disease. Qualitative analyses of various CTL responses have revealed substantial heterogeneity in the diversity of functions that are mobilized in response to antigen. Here, we studied the influence of the CD8 co-receptor, which is known to enhance antigen recognition by CTL, on the secretion of eight different cytokines and chemokines by human CTL clones using flow cytometric bead array. Our results show that abrogation of MHC class I/CD8 interactions exerts a differential influence on the distinct individual effector functions that are elicited in response to agonist ligands. The magnitude of this co-receptor blockade inhibitory effect was clearly related to the hierarchy of cytokine secretion in terms of activation threshold because those functions requiring the highest amounts of antigen were most affected. Thus, modulation of CD8 activity can effectively tune not only the sensitivity but also the qualitative profile of CTL responses.