Following acute lymphocytic choriomeningitis virus (LCMV) infection, there is a potent antiviral CD8 T–cell response that eliminates the infection. This initial CD8 T–cell response is followed by a period of memory during which elevated numbers of virus–specific CD8 T cells remain in the mouse. CD4 T cells are also activated after LCMV infection, but relatively less is known about the magnitude and duration of the CD4 response. In this study, we used intracellular staining for interferon–γ to measure both CD4 and CD8 responses in the same mice at the single cell level. After LCMV infection, there was an increase in the number of activated CD4 T cells and an associated increase in the number of virus–specific CD4 T cells. At the peak of this expansion phase, the frequency of virus–specific CD4 T cells was 1 in 20 (0.5–1.0 × 106 per spleen). Like the CD8 response, long–term CD4 memory could be found up to a year after the infection with frequencies of approximately 1 in 260 (0.5–1.5 × 105 per spleen). However, the magnitude of virus–specific CD8 T cells was greater than virus–specific CD4 T cells during all phases of the immune response (expansion, death, and memory). At day 8, there were 20– to 35–fold more virusspecific CD8 Tcells than CD4 Tcells. This initial difference in cell number lasted into the memory phase as there remained a ten– to 20–fold difference in the CD8 and CD4 responses. These results highlight the importance of the expansion phase in determining the size of the memory T–cell pool. In addition to the difference in the magnitude, the activation requirements of CD8 and CD4 T–cell responses were different: CD8 T responses were not affected by blockade of CD40– CD40 ligand interaction whereas CD4 responses were reduced 90%. So while there is long–term memory in both the CD8 and CD4 compartments, the rules regulating the activation of CD8 and CD4 T cells and the overall magnitude of the responses are different.