Although genetically different from its mother, a mammalian fetus bearing paternal alloantigens is normally not rejected. To investigate one of the many possible mechanisms involved in this important biologic phenomenon, we analyzed the consequences of fetal alloantigen recognition on maternal B lymphocytes. We used transgenic mice expressing a unique B cell receptor with a relatively high affinity for the MHC class I molecule H-2Kk on most B lymphocytes. We provide the first evidence for an alloantigen-specific B cell deletion in the spleens and bone marrow of transgenic mothers bearing H-2Kk-positive fetuses. This highly reproducible deletion affects < or =80% of Id-bearing B cells, starts at midpregnancy, and is only observed until term. Such a specific maternal B cell deletion could contribute to the success of the fetal allograft.