Neuroprotective peptides (SALLRSIPA [SAL] and NAPVSIPQ [NAP]) can prevent some alcohol-induced damage in fetal alcohol syndrome (FAS). Fractalkine, a chemokine constitutively expressed in the central nervous system reduces neuronal death from activated microglia. Using a model of FAS, we evaluated whether fractalkine is altered and whether NAP + SAL work through fractalkine.With an FAS model, C57BL6/J-mice were treated on gestational day 8 with alcohol (0.03 mL/g), placebo, or alcohol + peptides. Embryos were harvested after 6 hours and 10 days later. Fractalkine was measured in the protein lysate. Statistical analysis included the Kruskal-Wallis test.Fractalkine was significantly elevated at 6 hours (median, 341pg/mL; range, 263–424 pg/mL) vs controls (median, 228 pg/mL; range, 146–332 pg/mL; P < .001). NAP + SAL prevented the alcohol-induced increase (median, 137 pg/mL; range, 97–255 pg/mL; P < .001). Ten days later, fractalkine levels were similar in all groups (P = .7).Prenatal alcohol exposure acutely elevates fractalkine, perhaps in an effort to counter the alcohol toxicity. Pretreatment with NAP + SAL prevents the acute increase in fractalkine.