Specific immune suppression has been shown to be activated in culture by the interaction of primed and unprimed T cell subsets. The primed cell involved is found 8 days after immunization in spleen but not in lymph node or thymus cell populations. When the primed spleen cells were fractionated by nylon wool passage or anti-Thy-1 plus complement (C) treatment, prior to culture with unseparated unprimed cells, suppression was detectable only with primed B cells present in the co-cultures. Treatment of the primed spleen cells with anti-PC.1 (an antiserum specific for plasma cells) plus C eliminated their ability to cooperate with either unseparated or T cell-enriched populations of unprimed cells in suppressing the antibody response of the co-cultures. These data are consistent with the hypothesis that antibody-secreting plasma cells activate suppressor T cell precursors in cell populations not previously exposed to antigen.