The spontaneous appearance of anti-erythrocyte autoantibodies resulting in autoimmune hemolytic anemia described in NZB mice more than 40 years ago provided a model for the study of mechanisms behind the loss of self-tolerance. We developed an in vitro model of this anti-MRBC response in which CD8+ suppressor T cells were shown to be a controlling element. CD8+ T cells from young NZB mice co-cultured with spleen cells from old, actively autoimmune NZB mice suppressed the anti-MRBC responses of the old mice. Eliminating the CD8+ cells from young NZB spleen cells or even from non-autoimmune BALB/c spleen cells prior to culture removed the controlling influence of these CD8+ cells and allowed the development of anti-MRBC-secreting cells. This review will consider the role of the CD8+ suppressive cells in the anti-self-erythrocyte model in light of insights provided by current ‘regulatory T cell' literature.