The role of T lymphocytes in regulation of B cell responsiveness has been recognized for over a decade. Early studies assigned part of this regulation to a soluble product, initially designated T cell-replacing factor or TRF. Recently, investigators have discovered a level of factor complexity skillfully camouflaged by this simple term. Accordingly, the concept has now matured to encompass a battery of antigen non-specific, genetically unrestricted soluble factors which govern all aspects of B cell immunity: activation, proliferation, and differentiation. Here, we review our developing knowledge of this area. While many questions remain unresolved, there seems cause for optimism and a hope that increased understanding of these factors and their mode of action will eventually reveal the basis of B cell immunoregulation.