Six-day 'binge' ethanol intoxication postnatal days (PD) 4-9 delays up-regulation of γ-aminobutyric acid type A receptors (GABA A Rs) in developing rat septal neurons [Dev. Brain Res. 130 (2001) 25]. This distortion occurs during synaptogenesis and could contribute to cognitive dysfunction in fetal alcohol syndrome (FAS). Here, we asked two questions concerning requirements for vulnerability to GABA A R blunting by ethanol. First, we asked whether receptor blunting required PD 4-9 ethanol exposure in rat pups and found that just a brief 2-day exposure (PD 8-9) was as effective as all 6 days. However, 2-day exposure on PD 4-5 was ineffective, showing that 'binge' timing was important. We also asked whether 'binge' exposure directly inhibited intrinsic processes of septal neurons and could blunt GABA A Rs on cells maturing outside the brain. Embryonic septal neurons grown in serum-free dispersed culture developed extensive dendritic arborizations, spontaneous synaptic activity and robust whole-cell GABA A R function, but surprisingly, did not show developmental up-regulation of GABA A Rs like septal neurons maturing in vivo [Brain Res. 810 (1998) 100]. Furthermore, age-matched 6-day 'binge' ethanol exposure did not blunt GABA A R function in septal neurons in vitro. These results suggest developmental mechanisms driving up-regulation of GABA A R function in septal neurons in vivo briefly becomes vulnerable to ethanol insult in early postnatal life. While septal neurons express comparable functional GABA A Rs whether maturing in vivo or in vitro, vulnerability to ethanol-induced receptor blunting requires elements of an intact brain environment not replicated in culture.