We describe clones of hapten-specific inducer T cells from (BALB/c X A/J)F1 mice that respond to the p-azobenzenearsonate hapten conjugated to carrier proteins or directly conjugated to antigen-presenting cells. Some of the clones are also activated by haptens structurally related to arsonate. All activating analogues are recognized by each clone in association with the same major histocompatibility complex (MHC) protein as is arsonate. Weakly activating and nonactivating analogues are immunogenic in D2.GD amd (BALB/c X A/J)F1 mice, since they can effectively activate primed lymph node cells or long-term hapten-reactive cell lines. Hence the specificities of these clones may reflect their intrinsic recognition of arsonate and its analogues, rather than more efficient presentation of certain analogues than of others by antigen-presenting cells, or differential recognition of associated MHC epitopes by the clones. We compare the activation specificities of the clones with the binding specificities of monoclonal antibodies to arsonate, and discuss structural features of the analogues that may be important for activation and binding. Our results suggest that a site (or subsite) on arsonate-reactive T cell clones may interact directly with hapten, and may be experimentally separable from the site (or subsite) for MHC determinants.