Previous studies have indicated that a sizable fraction of adult human peripheral blood B cells may express IgM receptors encoded by somatically mutated V regions. From these studies it was uniquely associated with the peripheral blood B cell compartment, was uniquely associated with the peripheral blood B cell compartment, associated with particular VH gene segments and/or B cell subpopulations. We have addressed these issues by analyzing > 80 VH5 and VH6-encoded mu transcripts from unseparated peripheral blood, tonsil, and spleen B cells, as well as from B cells separated on the basis of CD5 Ag expression. The results demonstrate that somatically mutated VH5 and VH6 regions are ubiquitously expressed in IgM-bearing B cells in all peripheral adult human lymphoid organs, and that the occurrence of somatic mutations does not segregate with either CD5+ or CD5- B cell populations. The distribution and nature of mutations, as well as the occurrence of clonally related but divergent transcripts suggests that at least some of the mutations were selected by Ag.