The decline in the CD4% and CD4/CD8 ratios have been compared in lymph nodes and blood from SIV_MNE/E11S infected rhesus macaques. The results indicate that loss from the LN CD4⁺ cell pool does not occur until CD4/CD8 ratios of < 0.5 is reached in blood. These changes also correlate with the ability to isolate virus from the blood and the transition of CD45RA^hi to highly activated CD45RA^lo CD8⁺ cells both of which may play a role in eliminating CD4⁺ cells. In end‐stage disease, CD8⁺ cells also decline in LN and mitogen responsiveness no longer exists in any nodes. Interestingly at this stage, the circulating CD8% increases significantly and represents the only source of functional T cells remaining in the body.