Immune responses to hepatitis C virus (HCV) fail to clear the virus in most individuals. Why patients who are less likely to clear HCV infection have high plasma levels of CXCL10 (also known as IP-10), a chemokine that directs T cells to sites of infection, has long been unclear. In this issue of the JCI, Casrouge and colleagues shed light on this paradox by showing that CXCL10 in the plasma of many HCV patients is enzymatically processed to produce a CXCL10 receptor antagonist. These findings introduce a role for chemokine antagonism during HCV infection and unveil new avenues for improved HCV diagnosis and therapy.