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Immunocytochemical identification of antibody-forming cells (AFCs) in situ was used to test the hypothesis that the maintenance of chronic allotype suppression in heterozygous rabbits is the result of an autoimmune B-cell-mediated response. Appreciable numbers of B cells with antibody activity directed against the suppressed allotypic determinant were found in spleen and bone marrow sections of all chronically suppressed rabbits examined. Appropriate double-staining was used to determine that such cells were of the non-suppressed allotype. These cells were indistinguishable from antiallotypic AFCs found in larger numbers in spleens of normal heterozygous rabbits that had been immunized against a heterologous allotypic determinant, Auto-anti-allotypic AFCs were not found in suppressed rabbits less than 8 weeks old, nor were they found in normal (non-suppressed) heterozygous rabbits or chimeric rabbits formed by the injection of histocompatible but allotype mismatched lymphoid cells at birth. The findings reported here support the hypothesis that the long term maintenance of allotype suppression in the rabbit may result from the suppressive activities of autoimmune B cells. It is suggested that the suppression of an allotype during the first few weeks of life could result in a loss of tolerance to a self-determinant. The kinetics of auto-anti-AFC production support this idea in showing that such cells are generated following the decline of the antibody used to induce suppression. The triggering event may be the emergence of B cells expressing the previously suppressed gene product. [ABSTRACT FROM AUTHOR]