The data summarized herein demonstrate the utility of the low-affinity Fc epsilon R in delineating murine B-cell subsets. In the peritoneal cavity, the Fc epsilon R appears to be a reliable marker in distinguishing between conventional (Fc epsilon R+) and Ly-1/sister (Fc epsilon R-) B cells. In the spleens of normal animals, flow cytometric and histologic studies established that a distinct population of Fc epsilon R- B cells is also present and comprises the marginal zones. Thus in the spleen, the Fc epsilon R may be the first murine marker to allow for selective purification and analysis of marginal zone B cells. Although it is unlikely that splenic Fc epsilon R- B cells are directly related to peritoneal Fc epsilon R- Ly-1/sister B cells, further studies will be required to address this question. Analysis of autoimmune mice revealed that the splenic Fc epsilon R- subset is greatly expanded in these animals and indicates that the Fc epsilon R may be a sensitive indicator of abnormalities within the B-cell compartment. Additional studies compared the functional capacity of Fc epsilon R+ and Fc epsilon R- B cells and tested the ability of these populations to isotype-switch and respond to polyclonal stimuli. The results showed that Fc epsilon R+ and Fc epsilon R- B cells from both the peritoneum and spleen can switch to produce IgG, and all but the peritoneal Fc epsilon R- B cells can switch to the IgE class. This latter result is certainly interesting and demonstrates an important functional difference between peritoneal and splenic Fc epsilon R- B cells. Finally, experiments with B-cell mitogens showed further differences between the Fc epsilon R+ and Fc epsilon R- subsets. Whereas Fc epsilon R- B cells appeared to be more sensitive to LPS stimulation, Fc epsilon R+ B cells were clearly more responsive to an anti-IgM signal. Taken together, the results show that the Fc epsilon R is likely to be useful in separating B cells with different phenotypic, histologic, and functional characteristics.