Children prenatally exposed to alcohol typically exhibit behavioral abnormalities, including hyperactivity, learning deficits, and an increased prevalence of depression. Similar impairments are found in children of hypothyroid mothers, and we have shown that alcohol-consuming rat dams have suppressed hypothalamic-pituitary-thyroid (HPT) function. Therefore, we hypothesized that suppressed maternal thyroid hormonal milieu may contribute to the deleterious consequences of prenatal alcohol exposure. We aimed first to confirm and then to reverse the behavioral deficits in the fetal alcohol exposed (FAE) rat offspring by administration of thyroxine (T4) to the alcohol-consuming dams. Adult offspring prenatally exposed to ethanol (FAE; 35% ethanol-derived calories), pair-fed (PF) or control (C) diets were tested in the Morris water maze (MWM), the forced swim test (FST), and the open field test (OFT) to assess spatial learning, depressive behavior, and exploratory behavior/anxiety, respectively. Adult FAE offspring took longer to locate a hidden platform in the MWM and showed increased depressive behavior in the FST both of which were reversed by administration of T4 to the alcohol-consuming mother. We found sex and brain regionspecific alterations in expression of genes involved in these behaviors in FAE adult offspring. Specifically, decreased hippocampal GAP-43 mRNA levels in adult FAE females and decreased glucocorticoid receptor (GR) expression in the amygdala of male and female FAE offspring were observed. The decreased mRNA levels of GAP-43 and GR were normalized by T4 treatment to the alcohol-consuming mother. Our results suggest that the suppressed HPT function of the alcohol-consuming mother contributes to the behavioral and cognitive dysfunctions observed in the offspring. Prenatal alcohol exposure has long-term developmental consequences, 1-3 and in humans alcohol is recognized as a teratogen leading to long-lasting CNS dysfunctions. 4 Specifically, patients with fetal alcohol exposure (FAE) have marked cognitive deficits, including difficulty focusing and sustaining attention, 5 and place learning deficits in a virtual Morris water task. 6 Attention deficit hyperactivity disorder (ADHD) is frequently diagnosed in FAE children. These neurocognitive and behavioral characteristics differ between FAE children and those with a primary diagnosis of ADHD, as FAE children have difficulties primarily in the encoding and retrieval of information. 7 A significantly increased prevalence of depression is also found in children 8 and adults 9 prenatally exposed to alcohol. It is important to note that, in contrast to the higher female prevalence of depressive disorders in the general population, the rate of depression found in adults with prenatal alcohol exposure was nearly equal among men and women. 9 Fetal alcohol effects qualitatively similar to those described in children with a history of gestational alcohol exposure have been detected with animal models. 10 Cognitive deficits have been found in FAE animal models...