We have examined the expression of a cell surface antigen by B lineage cells in human fetuses, newborns and adults using a newly produced monoclonal antibody, HB-7. The HB-7 antigen was found to be a protease sensitive 45,000 MW molecule that appeared to be the same molecule recognized by the OKT-10 antibody. The HB-7 reactive molecule was expressed by all fetal pre-B and B cells, and 50% of newborn blood and adult bone marrow B cells. In contrast, only a small minority of B cells (2-12%) from blood, spleen and tonsil of adults were weakly HB-7+. The pokeweed mitogen-responsive B cell precursors of plasma cells were also HB-7-, but the HB-7 antigen was re-expressed during the plasma cell stage. We conclude that this antigen is unique among known B cell differentiation antigens in its intermittent pattern of expression during B cell development. The reactivity of the HB-7 antibody with immature, but not mature, B cells makes it well suited for studies of B cell ontogeny.