third segment of the antennae (R.L. French, personal communication). Exposing flies to ethanol vapor under conditions identical to those used for our microarray study resulted in blackening of only 0.5% of antennae (n = 216). These data suggest that the down-regulation of olfactory genes by ethanol exposure occurs at lower ethanol concentrations than those that cause visible tissue damage. Moreover, expression of the OR gene Or43b, and the antennal-specific genes OS9 and pinocchio were not decreased following ethanol exposure (Table S1; Morozova et al., 2006; Raha and Carlson, 1994; Rollmann et al., 2005). Down-regulation of olfactory genes could serve as a general protective mechanism against ethanol-induced excitotoxicity. Consistent with decreased olfactory function in ethanol-exposed flies, we found that the magnitude of the olfactory startle response was reduced during the second ethanol exposure (PS decreased from 8.8 mm/s for exposure 1 to 7.4 mm/s for exposure 2, p = 0.007, paired t-test).