Class II molecules of the major histocompatibility complex play an important role in mediating cellular interactions and are differentiation antigens on lymphobohematopoietic cells. We have previously characterized a human B-cell line (BALM-3) whose cells fail to express HLA class II molecules unless treated with phorbol acetate (TPA). Recently, we identified a spontaneous variant of BALM-3 whose cells express HLA class II molecules in the absence of TPA. Since normal B cells lose HLA class II molecules on terminal differentiation, these two BALM-3 cell populations may provide a model for a discrete phase of B-cell maturation. Alternatively, they may reflect two B-cell activation states characterized by quantitative differences in their expression of class II molecules. Expression of six of 22 additional surface molecules (HLA class I, CD23, p60, p124, p129, p141) increases by a factor of three or more as BALM-3 cells spontaneously acquire class II molecules while that of one of the 22 (p45) decreases by a comparable amount. Expression of the plasma cell-associated T10/CD38 antigen decreases by a factor of two. These additional surface molecules might also reflect lymphoid differentiation/activation antigens and/or participate in HLA class II-mediated cellular interactions and require further study. Use of TPA to induce the expression of HLA class II molecules produces similar changes in several but not all of these surface antigens.