Abstract The present study examined whether halothane anesthesia could alter immunoregulation in autoimmune disease-prone BXSB Mp and MRL Mp mice. This was judged by histopathological examination of lymph nodes and by studies on mitogen-induced transformation of splenic lymphocytes. The development of lymphoma-like disease in BXSB males and the appearance of lymphoproliferation and systemic lupus erythematosus-like disease in MRL Mp lpr lpr mice were revealed by histologic examination of lymph nodes and other tissues and by identification of immune complexes in kidney sections by immunofluorescence. Splenic lymphocytes from MRL Mp +/+ mice exposed to halothane showed a 44% reduction in mean stimulation indices (MSI) compared to exposure to O 2. Likewise, the MSI of splenic lymphocytes from MRL Mp lpr lpr mice exposed to halothane were reduced to 42% when compared with those from MRL Mp lpr lpr mice subjected to O 2. In accord with the MRL results, halothane induced a 38% reduction in the stimulation indices of autoimmune and lymphoma-like disease-prone BXSB mice and a 27% decline in the lymphocyte proliferative responsiveness of autoimmune disease-insusceptible control C57B1 6 mouse spleen cells, compared to their respective O 2 control values. Results demonstrate that halothane facilitated an earlier onset in loss of immunoregulation associated with development of autoimmunity and lymphomagenesis in genetically disease-prone mice receiving halothane than in those receiving oxygen.