We have tested several structurally related haptens, conjugated to ovalbumin, for their effect on activation of an inducer T-cell clone reactive to the p-azobenzenearsonate (arsonate) hapten. Low concentrations of some analogs inhibited DNA synthesis and lympkokine production by the clone in response to arsanylated antigen, but not in response to the lectin concanavalin A. Inhibition was specific for this clone, since the response of clones reactive to other antigens was not blocked. Inhibition may result from competition of these analogs with arsonate at a site on the T cell. The effectiveness of blocking by arsonate analogs parallels their ability to bind to a previously described arsonate-binding site on the clone (Rao et al., accompanying paper). We suggest that the binding and blocking assays detect the same physiological arsonate-recognition site on the clone, and hence that the cell-surface arsonate-binding sites we have described mediate its physiological response to antigen.