Prenatal alcohol exposure can affect brain development, leading to behavioral problems, including overactivity, motor dysfunction and learning deficits. Despite warnings about the effects of drinking during pregnancy, rates of fetal alcohol syndrome remain unchanged and thus, there is an urgent need to identify interventions that reduce the severity of alcohol's teratogenic effects. Insulin-like growth factor-I (IGF-I) is neuroprotective against ethanol-related toxicity and promotes white matter production following a number of insults. Given that prenatal alcohol leads to cell death and white matter deficits, the present study examined whether IGF-I could reduce the severity of behavioral deficits associated with developmental alcohol exposure. Sprague-Dawley rat pups received ethanol intubations (5.25 g/kg/day) or sham intubations on postnatal days (PD) 4-9, a period of brain development equivalent to the third trimester. On PD 10-13, subjects from each treatment received 0 or 10 microg IGF-I intranasally each day. Subjects were then tested on a series of behavioral tasks including open field activity (PD 18-21), parallel bar motor coordination (PD 30-32) and Morris maze spatial learning (PD 45-52). Ethanol exposure produced overactivity, motor coordination impairments, and spatial learning deficits. IGF-I treatment significantly mitigated ethanol's effects on motor coordination, but not on the other two behavioral tasks. These data indicate that IGF-I may be a potential treatment for some of ethanol's damaging effects, a finding that has important implications for children of women who drink alcohol during pregnancy.