To test the importance of B lymphocytes in immunity to major histocompatibility complex class I alloantigens, B cell-deficient mice were generated by reconstituting severe combined immunodeficiency mice, which lack functional B and T lymphocytes, with T cells or with both T and B cells. The reconstituted mice were challenged with a cancer that expresses an MHC class I alloantigen at a low level and is susceptible to killing by CD8+ cytotoxic T lymphocytes. Tumors grew more slowly in and were rejected more frequently by the mice lacking B cells. Understanding the mechanism by which B cells suppress tumor allograft rejection may lead to new approaches for suppressing immune attack on transplanted tissues.