The injection of syngeneic activated T cells into rodents can induce a T cell response against activation markers of the T cells, ergotopes. The responding anti-ergotypic T cells have been shown to suppress experimental autoimmune encephalomyelitis (EAE). This paper reports the characteristics of the anti-ergotypic response. It was found that irradiated activated T cells were as good as untreated living activated T cells in inducing anti-ergotypic cells in vivo. Glutardialdehyde-fixed (0.3%) cells were poor stimulators in vivo and non-stimulatory in vitro. Dilution of glutardialdehyde to 0.003% before fixation preserved the stimulatory capacity in vitro. Fixation or irradiation of T cells at different times after activation showed that the stimulatory ergotope appears only after more than 12 h of activation. This ergotope is not secreted by activated T cells, but is a structural component of the activated T cell. Injection of solubilized proteins from activated T cells, but not of supernatants from activated T cells, was able to induce an anti-ergotypic response in vivo. In vitro supernatants from activated T cells also were not stimulatory to anti-ergotypic T cells. The anti-ergotypic response could be measured in draining lymph nodes 3 days after injection, reached a maximum after 7-10 days and subsided thereafter. It was earlier and stronger than the anti-idiotypic response. Induction of the response was dose dependent. As few as 100 cells were able to induce a marked anti-ergotypic response. The ease of the induction and the strength of the anti-ergotypic response suggest a physiological role in immunoregulation.