Neuroprotective peptides (NAP+SAL) can prevent some alcohol-induced damage in fetal alcohol syndrome(FAS). Fractalkine, a chemokine constitutively expressed in the CNS reduces neuronal death from activated microglia. Using a model of FAS we evaluated if fractalkine is altered and if NAP+SAL work through fractalkine.Using a 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 6h(E8) and 10 days later(E18). Fractalkine was measured in the protein lysate (Luminex xMAP). Statistical analysis included Kruskal-Wallis.Fractalkine was significantly elevated at 6h (median 341 pg/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, range 97-255 pg/ml, P<.001). At E18, fractalkine levels were similar in all groups (P=0.7).Prenatal alcohol exposure acutely elevates fractalkine, perhaps in an effort to counter the alcohol toxicity. Pre-treatment with NAP+SAL prevents the acute increase in fractalkine.