The transcriptional repressor Bcl6 controls development of the follicular Th cell (T FH) lineage, but the precise mechanisms by which Bcl6 regulates this process are unclear. A model has been proposed whereby Bcl6 represses the differentiation of T cells into alternative effector lineages, thus favoring T FH cell differentiation. Analysis of T cell differentiation using Bcl6-deficient mice has been complicated by the strong proinflammatory phenotype of Bcl6-deficient myeloid cells. In this study, we report data from a novel mouse model where Bcl6 is conditionally deleted in T cells (Bcl6 fl/fl Cre CD4 mice). After immunization, programmed death-1 (PD-1) high T FH cells in Bcl6 fl/fl Cre CD4 mice are decreased> 90% compared with control mice, and Ag-specific IgG is sharply reduced. Residual PD-1 high CXCR5+ T FH cells in Bcl6 fl/fl Cre CD4 mice show a significantly higher rate of apoptosis than do PD-1 high CXCR5+ T FH cells in control mice. Immunization of Bcl6 fl/fl Cre CD4 mice did not reveal enhanced differentiation into Th1, Th2, or Th17 lineages, although IL-10 expression by CD4 T cells was markedly elevated. Thus, T cell–extrinsic factors appear to promote the increased Th1, Th2, and Th17 responses in germline Bcl6-deficient mice. Furthermore, IL-10 may be a key target gene for Bcl6 in CD4 T cells, which enables Bcl6 to promote the T FH cell phenotype. Finally, our data reveal a novel mechanism for the role of Bcl6 in promoting T FH cell survival.