The present study is a survey of classes of self determinants that are recognized in association with the trinitrophenyl hapten (TNP) by human T cell effectors sensitized in vitro with TNP-modified autologous cells. Specificity was investigated by studies of direct lysis and cold target cell competition. Interpretation of the results of direct lysis experiments was facilitated by the use of interaction analysis. Studies of effector populations from six siblings demonstrated that on the average approximately 40% of the cytotoxic activity was specific for polymorphic determinants of which most or all were HLA linked. Studies of effectors from six unrelated donors, selectively matched for HLA-A and -B locus determinants, demonstrated that some of the cytotoxic activity was directed against HLA-A and/or -B locus-associated polymorphic determinants, but that the serologically-defined HLA-A and -B locus antigens were not the only polymorphic determinants recognized. Studies by cold target cell competition demonstrated that some of the cytotoxic activity was directed against TNP in association with relatively nonpolymorphic antigens. Thus, there was evidence for considerable diversity of the classes of self determinants that human T cells can recognize in association with TNP. Furthermore, the possibility of immune response gene control of the cytotoxic response to these determinants was suggested by differences between donors in their response to TNP-modified self determinants.