Sir: A number of investigators have recently reported that cell membranes, or solubilized proteins derived from them, are capable of inducing cytotoxic responses in secondary cultures (1–6). They have implied thereby that they are gaining insight into the specificity of the structures recognized by cytotoxic T cells. An alternative interpretation seems equally plausible: that the membrane preparations act not directly on cytotoxic memory cells, but rather on helper T cells, which, by secreting soluble mediators, “trigger” cytotoxic cell differentiation. This interpretation is supported by several recent reports. Thus, Ryser et al. (7), Wagner and Rollinghoff (8), and this laboratory (Okada et al., in press) have shown that cell mediators secreted by primed Lyt I+ T cells can cause the direct differentiation of cytotoxic T cells in secondary (memory) cultures. Moreover, the specificity of the cytotoxic cells induced by these mediators is that of the antigen initially used for priming.