Class R inhibitory oligonucleotides (INH-ODNs) show lower potency for resting mouse and human B cells. Total CD43- B cells from C57BL6 mice were stimulated with class B(K) CpG-ODN 1826 for either 18 to 42 hours (a-c) or 6 days (d) in the presence of increasing concentrations of INH-ODNs (1 to 1,000 nM). Percentage of cells with hypodiploid DNA content and cells entering the G1-M phase of the cell cycle was determined in acridine orange flow cytometry. Interleukin-6 (IL-6) and polyclonal IgM were measured in enzyme-linked immunosorbent assay (ELISA) (n = 3 to 7). (e) Total mouse B cells were stimulated with PO-CpG-ODN for 6 days. (f) Total human Namalwa B cells were stimulated with human PS-CpG-2006 for 42 hours. CD86 expression and polyclonal IgM secretion were measured. Indicated class R and B INH-ODNs were added over the concentration range shown (n = 3 or 4). *P < 0.05. PO, phosphodiester; PS, phosphorothioate.