Eastern fence lizards (Sceloporus undulatus) are physiologically stressed by predatory venomous invasive fire ants (Solenopsis invicta). We examined how history of invasion (and associated stress) and acute stress treatment affected the cell-mediated immune response of lizards. Lizards from invaded sites had reduced immune response compared to those from uninvaded sites. Acute stress treatment affected lizards from invaded but not uninvaded sites, suggesting that evolutionary history of stress alters the immune response to short-term stress.