In Brown‐Norway (BN) rats mercuric chloride induces an autoimmune disease characterized by an increase in serum IgE concentration, and by the production of anti‐glomerular basement membrane antibodies responsible for a glomerulonephritis with a heavy proteinuria. (i) This disease results from a B‐cell polyclonal activation probably due to frequent anti‐class II T cells. (ii) The self limitation observed in this model is associated with both a decrease in the frequency of anti‐class II T cells and the emergence of CD8+ T cells able to suppress these autoreactive T cells. (iii) In Lewis (LEW) rats which do not develop autoimmunity, HgC12 provokes the appearance of non‐antigen‐specific CD8+ T cells responsible for a depression of T‐cell functions. The aim of this work was to test the effect of treatment with an anti‐CD8 monoclonal antibody (MoAb) in both BN and LEW rates, Anti‐CD8 MoAb‐treated rats were effectively depleted in CD8+ T cells. However, neither the induction nor regulation phases of mercury‐induced autoimmunity were modified in BN rats. Mercury‐induced immunosuppression in LEW rats was abrogated; however, depletion in CD8+ T cells did not allow the disease to occur in that strain. Finally, CD8 depletion induced in normal BN rats rats the appearance of rare anti‐class II T cells showing that these cells are normally present in that strain but negatively contr