BAZF, a member of the Bcl6 gene family, acts as a sequence-specific transcriptional repressor in association with Bcl6. However, the tissue expression pattern of BAZF differs from that of Bcl6, suggesting a Bcl6-independent function of BAZF. In order to examine the physiological function of BAZF, we generated BAZF-deficient mice and transgenic mice with BAZF-cDNA under the control of the lck proximal promoter (lck-BAZF). These mice were viable and no gross anatomical abnormalities were observed after birth. Since Bcl6 is a key molecule for the generation of memory T cells, we examined the function of T cells of these mice. We show here that cell proliferation of naive CD4 T cells, but not memory ones, of BAZF-deficient mice to anti-CD3 antibody stimulation was impaired. Conversely, cell proliferation of naive CD4 T cells, but not memory ones, of lck-BAZF mice was augmented. Since cell proliferation of naive CD4 T cells of lck-Bcl6 mice to anti-CD3 antibody stimulation was severely impaired, BAZF may attenuate the regulatory effect of Bcl6 on antigenic activation of naive CD4 T cells by Bcl6/BAZF heterodimer formation. These results suggest that BAZF is necessary for activation of naive T cells to antigenic stimulation.