This study demonstrates that several substances which raise intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels in different ways were able to enhance both RNA and DNA synthesis in mouse purified B cells co-stimulated by the protein kinase C activator phorbol 12-myristate 13-acetate and the Ca2+ ionophore ionomycin, while earlier activation events were not modified. These included early changes in cell size and chromatin decondensing demonstrated by light scatter properties at narrow and 90 degrees angles, increase in Ia expression and loss of surface IgD. We concluded that cAMP can up-regulate mouse B cell activation by controlling progression into the late G1 (G1B)/S phase, but not transition from G0 to early G1 (G1A). Furthermore, because cAMP could synergize with ionomycin but not with phorbol 12-myristate 13-acetate to induce RNA and DNA synthesis, we proposed that the cAMP effects in this model may be related to the protein kinase C pathway.