In this and the accompanying paper we examine the nature of the interactions between effector cells and target cells leading to lysis in T cell-mediated cytolysis reactions. In the first paper, we re-examine the role of lectin (Con A) in the process of lectin-dependent cell-mediated cytotoxicity (LDCC). Lectin has generally been thought to act simply as a bridge between the cytotoxic effector cell (EC) and the target cell (TC), thus bypassing the need for receptor-antigen interaction and accounting for the nonspecific character of this lytic reaction. A role for lectin in the activation of cytotoxic function in the EC has also been suggested. In this paper we confirm that LDCC occurs when TC alone are pretreated with lectin, but not when EC alone are pretreated with lectin, unless free lectin is also present in the assay mixture. In addition, we demonstrate that the failure of lectin-pretreated EC to bind to and lyse TC is not caused by agglutination or self-destruction of the EC. Moreover, lectin-pretreated EC are not inherently deficient in the ability to bind or lyse TC, if the latter are pretreated with lectin, or if free lectin is present in the assay. Finally, when EC are used as both effectors and targets in LDCC, lysis is observed only in the direction of the lectin-pretreated partner. From these results we conclude that in LDCC, as in specific CTL cytolysis, CTL-TC recognition proceeds through interaction of an EC surface receptor (distinct from the lectin receptor), and a TC antigen perhaps modified by, but distinct from, the lectin itself. In the accompanying paper we present evidence that this receptor-determinant interaction involves TC MHC antigen.