A two-dose alcohol challenge protocol was used to study genetic influences on the acute adaptation of the EEG to alcohol in 53 monozygotic and 38 same-sex dizygotic Caucasian twin pairs averaging 30 years of age. Equal doses of alcohol were administered at 10:00 and 11:00 AM, yielding mean peak breath alcohol concentrations of 0.057% and 0.099%, respectively. Eyes-closed, resting EEG was recorded four times: at baseline; on the ascending limb of the overall experiment at a breath alcohol concentration (BrAC) near 0.06%; on the descending limb at a BrAC near the value when the subject's EEG was obtained on the ascending limb; and, finally, when the BrAC fell to 0.02%. Genetic analyses of log-transformed values of total spectral power (L10TSP) and spectral band power (L10SBP) were performed on EEG spectra averaged across all 17 scalp lead locations. After adjusting for body weight, a significant fraction of population variance in L10TSP was attributable to genetic influence: H2 values for TSP were 0.73, 0.72, and 0.73 at the three postalcohol EEG recordings, respectively. Similar findings pertained to each L10SBP at each postalcohol recording, except forthe delta band. The change in postethanol EEG power was examined for evidence that genes influence acute adaptations in brain function. Descending-minus-ascending limb L10TSP was normalized by the individual's ascending limb L10TSP to minimize nonalcohol-related effects that can influence both measurements. Earlier analyses of the same sample's initial EEG response to alcohol noted a substantial increase in the ascending limb EEG power, compared with baseline. Thus, positive values of the postethanol change denote a progression away from baseline attributable to acute sensitization to alcohol; negative values signify a return toward baseline values suggesting acute tolerance to alcohol. Genetic analysis of the normalized difference in L10TSP had a highly significant H2 value of 0.70, indicating that both acute tolerance and acute sensitization to alcohol may represent adaptations reflecting substantial heritable influence. Slightly smaller, but significant values of H2 for the normalized difference in L10SPB were observed for delta, alpha-slow and beta-slow frequency bands. In contrast, H2 for the differences between the final and ascending limb EEG power were not significant, except for the theta band. Thus, heritable drowsiness may have contributed to detection of genetic influences on acute adaptation, but represent a potential confound only in the theta band.