We and others have recently found that mature murine B cells can be induced to undergo apoptosis, in vitro, in a dose-dependent manner, by extensive crosslinking of membrane IgM with polyclonal anti-mu. During the analysis of tolerance in transgenic mice expressing rearranged IgM or IgM + IgD receptors, we observed that, Sp6 anti-TNP Ig and anti-MHC transgenic splenocytes, would undergo receptor-mediated apoptosis in vitro just like their normal, non-transgenic littermates. However, transgenic mice expressing rearranged receptors typical of B1 cells, not only contained large numbers of CD5+ cells in their spleens, but these cells failed to undergo apoptosis under conditions that led to programmed cell death in normal splenocytes. B1 spleen cells also failed to proliferate with anti-IgM, although the responsiveness of cells from the other transgenic lines varied depending on the background strains. These differences are due in part, to strain differences, but they also imply that the response pattern of transgenic B cells reflects not only the subset composition in this organ, but also the transgenic specificity of the receptor.