The number of virus-specific CD8 T cells increases substantially during an acute infection. Up to 90% of CD8 T cells are virus specific following lymphocytic choriomeningitis virus (LCMV) infection. In contrast, studies identifying virus-specific CD4 T cell epitopes have indicated that CD4 T cells often recognize a broader array of Ags than CD8 T cells, consequently making it difficult to accurately quantify the total magnitude of pathogen-specific CD4 T cell responses. In this study, we show that CD4 T cells become CD11a hi CD49d+ after LCMV infection and retain this expression pattern into memory. During the effector phase, all the LCMV-specific IFN-γ+ CD4 T cells display a CD11a hi CD49d+ cell surface expression phenotype. In addition, only memory CD11a hi CD49d+ CD4 T cells make IFN-γ after stimulation. Furthermore, upon secondary LCMV challenge, only CD11a hi CD49d+ memory CD4 T cells from LCMV-immune mice undergo proliferative expansion, demonstrating that CD11a hi CD49d+ CD4 T cells are truly Ag specific. Using the combination of CD11a and CD49d, we demonstrate that up to 50% of the CD4 T cells are virus specific during the peak of the LCMV response. Our results indicate that the magnitude of the virus-specific CD4 T cell response is much greater than previously recognized.