The phenotype of B lineage cells (TdT+, pre-B, IgM+, IgD-, and IgM+,IgD+) in infant and adult human bone marrow was compared with that of B cells seen in peripheral tissues such as tonsil and blood. The range of B cell-associated antibodies used included four reagents with greater than 90% reactivity on peripheral B cells: RFB4 and To15 (both p135, corresponding to CD22), RFB6 (p140 corresponding to CD21), and Y29/55, a unique B cell-specific antibody. In addition, AL-1, an antibody with virtually no reactivity against peripheral B cells was also used. The BM cell subpopulations were heterogeneous in respect of antibody reactivity. The TdT+, pre-B and IgM+, IgD- cells were AL-1+ but did not express membrane antigens recognized by the antibodies To15, RFB4 (CD22), and RFB6 (CD21). TdT+, pre-B cells, and 50% of IgM+, IgD- BM B cells were also unreactive with antibody Y29/55, the other 50% being Y29/55+. In contrast, the IgM+,IgD+ BM B cells, like peripheral B cells, were positive with antibodies To15, RFB4, RFB6, and Y29/55, but reacted only in small numbers with AL-1. The orderly differentiation-linked display of these antigens was also suggested by the findings that normal TdT+, pre-B, and IgM+,IgD- cells expressed the To15 and RFB4 (CD22) antigens in their cytoplasm (in the Golgi region). This observation was confirmed in malignant common acute lymphoblastic and pre-B blast cells, as well as in the corresponding permanent cell lines KM3 and NALM-6. In these lines the membrane expression of To15 and RFB4 could be induced by phorbol ester during a 48 to 72 hr culture period.