Specific antigen-binding cells from spleens of immune and nonimmune mice were isolated by the method of fiber fractionation. After removal from the fibers, these cells were assayed for their viability, their ability to rebind to fibers of the same specificity, and their in vivo response to the antigen after transfer to syngeneic irradiated recipients. These experiments indicate that the fiber method yields highly enriched populations of specific antigen-binding cells that are viable and include antigen-sensitive bone marrow-derived cells capable of undergoing mitosis and differentiating into antibody-secreting cells.