Cerebrospinal fluid (CSF) samples were collected from monkeys infected with SIV_mac251 (SIV) or HIV-1/ SIV_mac chimeric viruses (SHIV_HXBc2 and SHIV_89.6P) to investigate quinolinic acid (QUIN) levels in the intrathecal compartment. CSF levels of QUIN were elevated in the SIV-infected monkeys, especially in animals with end-stage disease, and in those infected with pathogenic SHIV_89.6P, but not after infection with the non-pathogenic construct SHIV_HXBc2. QUIN elevations occurred in association with reduced CD4⁺ and increased CD8⁺ lymphocytes, cellular alterations that were more pronounced in CSF than in the blood. These findings support the view that the intrathecal compartment provides a unique window on viral infection, and are in keeping with the a priori prediction that QUIN increases primarily in response to more pathogenic viral strains.