Human peripheral blood lymphocytes can be phenotypically identified by the presence of one or both of two proteins, 225,000-dalton macromolecular insoluble cold globulin (225-MICG) and 185,000-dalton MICG (185-MICG). T cells synthesize and insert into their plasma membrane 225-MICG, null cells 185-MICG, and B cells both 225 and 185-MICG. In contrast, the monoclonal B cells of chronic lymphocytic leukemia are characterized by the presence of 225-MICG and the absence of 185-MICG. We have recently found it possible to chemically deplete 185-MICG from viable normal B cells by treating them with diisopropylfluorophosphate (DFP), thus making normal B cells phenotypically resemble leukemic cells. In the present report we determined whether certain peculiar properties of these leukemic cells would be associated with the normal B cells chemically depleted of 185-MICG. In normal B cells, SIg diffuses in the lipid bilayer to form clusters and caps under appropriate conditions, while in chronic lymphocytic leukemia (CLL) cells this does not occur. Normal B cells depleted of 185-MICG fail to undergo capping of SIg or surface MICG under appropriate conditions. Both DFP-treated B cells and CLL cells tend to rupture when smeared on a glass slide. Both CLL cells and DFP-treated B cells fail to secrete 225-MICG after it has been synthesized intracellularly. The relationship of these findings to the mechanisms of secretion and capping are discussed.