Previous studies have shown that TNP-LPS-induced B memory cells can be recalled by either TNP-LPS or DNP-Ficoll and that cyclosporin A (CsA) prevents the expression of these B memory cells when DNP-Ficoll and not TNP-LPS is the challenging antigen. The possibility that the mitogenic signal delivered by TNP-LPS circumvents the inhibition exerted by CsA was investigated. It is demonstrated here that TNP-LPS, in its non-mitogenic (polymyxin-B-treated) as well as in its mitogenic form, is capable of driving TNP-specific B memory cells into the antibody-secreting stage, regardless of the presence or absence of CsA. It is suggested that both forms of TNP-LPS activate the same CsA-resistant subpopulation of B memory cells. The lack of DNP-Ficoll-induced memory expression in the presence of CsA is related to an intrinsic sensitivity to CsA inhibition of a subpopulation of B memory cells.