Constitutive expression of the c-fos gene perturbs the de novo synthesis of RNA and DNA in B cells stimulated by surface immunoglobulin (sIg) cross-linking. In order to examine kinetics of the regulatory effect on the activation process of B cells, we used splenic B cells from transgenic mice carrying the c-fos gene under the control of the interferon alpha/beta (IFN)-inducible Mx gene promoter (Mx-c-fos). In the absence of IFN, Mx-c-fos B cells proliferated well by anti-IgM stimulation. However, both RNA and DNA synthesis in the Mx-c-fos B cells were markedly reduced by the addition of IFN in the culture within 12 h after anti-IgM stimulation. These results suggest that this regulatory effect of c-Fos displays at the mid G1 phase of the cell cycle.