Abstract Injection of trinitrophenyl (TNP)-modified splenocytes (TNP-Sp) into the anterior chamber of the eye results in systemic tolerance to TNP, a phenomenon termed anterior chamber associated immune deviation (TNP-ACAID). Two distinct suppressor pathways develop after the induction of TNP-ACAID. The primary suppressor pathway (I) is antigen-specific, is mediated by a cyclophosphamide (Cy)-sensitive suppressor T cell (Ts-I), and requires a Cy-sensitive auxillary cell. The secondary suppressor pathway (II) is antigen nonspecific, is mediated by a Cy-resistant suppressor T cell (Ts-II), and requires a TNP-pulsed accessory macrophage. Suppression via pathway II is demonstrable only when Ts-I cells are functionally inactivated by Cy. Furthermore, the addition of T cells from Sp containing active Ts-I inhibits Ts-II. This suppression of a suppressor cell (i.e., contrasuppression) is mediated by either Ts-I or a third T cell population, which is also Cy sensitive.