Alcohol is a teratogen that causes damage to the developing fetus. Prenatal alcohol exposure can cause physical deformities, neuropathology, and behavioral alterations. In addition to hyperactivity and impairments in motor, social, attention and learning domains, prenatal alcohol exposure may lead to increased alcohol preference later in life. Thus, the same children exposed to alcohol during fetal life may experiment with alcohol during adolescence - a period of development when the brain is also particularly vulnerable to alcohol. It is not known, however, whether prenatal alcohol exposure influences the vulnerability of the adolescent brain to alcohol-induced pathology and subsequent behavioral alterations. The present study used a 2 (neonatal alcohol exposure, control) x 2 (adolescent alcohol exposure, control) x 2 (male, female) design. Sprague-Dawley rats received ethanol exposure (2.5 g/kg/day) or sham intubations from postnatal days (PD) 4-9, a period of development equivalent to the third trimester. Subjects were then exposed to ethanol (4.0 g/kg/day) or sham intubations during adolescence from PD 28-42 on a 2 day on / 1 day off schedule. Mean blood alcohol concentrations (BAC) were around 200 mg/dl during both developmental periods. During early adulthood, subjects were tested on tasks that depend on the functional integrity of the hippocampus and prefrontal cortex, areas of the brain that are sensitive to alcohol exposure. Spatial learning was measured in a Morris water maze task on PD 52-60, and contextual and conditioned stimulus learning was measured with a trace fear-conditioning task on PD 63-64. Alcohol exposure during each developmental time period alone was not expected to robustly impair behavior, but it was hypothesized that subjects exposed to alcohol during both developmental periods would show significant impairments on behavioral tasks. Unexpectedly, neonatal alcohol exposure produced significant neuropathology, reducing both forebrain and cerebellar weight. Consistent with gross neuropathology, neonatal alcohol significantly slowed acquisition of trace fear conditioning in both males and females and slowed acquisition in spatial learning in males. In contrast, adolescent alcohol exposure did not significantly induce gross brain pathology or disrupt learning. These data suggest that 200 mg/dl/day ethanol is sufficient to disrupt cognitive development during the 3rd trimester equivalent but not during adolescence. Females exposed to alcohol during adolescence did, however, exhibit an increased conditioned fear response to the conditioned stimulus once the response was learned, suggesting alterations in emotional responding. Finally, the combination of neonatal and adolescent alcohol exposure did not alter these patterns with one exception. Male subjects exposed to alcohol during both developmental periods spent less time in the periphery of the Morris water maze tank (thigmotaxis), which may indicate that combined alcohol exposure during the prenatal and adolescent periods reduced anxiety or increased risk taking in a sex-dependent manner. Thus, these data suggest that prenatal alcohol exposure does not increase risk for cognitive deficits, but may affect emotional consequences of adolescent alcohol exposure, at least with the alcohol exposure parameters used in the present study. Future studies should more specifically examine the effects of combined prenatal and adolescent alcohol exposure on stress and emotional development.