Modern psychopharmacological research in humans focuses on how specific psychoactive molecules modulate oscillatory brain activity. We present state-of-the-art EEG methods applied in a resting-state drug study. Thirty healthy male nonsmokers were randomly allocated either to a nicotine group (14 subjects, 7 mg transdermal nicotine) or a placebo group (16 subjects). EEG activity was recorded in eyes-open (EO) and eyes-closed (EC) conditions before and after drug administration. A source reconstruction (minimum norm algorithm) analysis was conducted within a frequency range of 8.5-18.4 Hz subdivided into three different frequency bands. During EO, nicotine reduced the power of oscillatory activity in the 12.5- to 18.4-Hz frequency band in the left middle frontal gyrus. In contrast, in the EC condition, nicotine reduced the power in the 8.5- to 10.4-Hz frequency band in the superior frontal gyri and in the 10.5- to 12.4-Hz and 12.5- to 18.4-Hz frequency bands in the supplementary motor areas. In summary, nicotine reduced the power of the 12.5- to 18.4-Hz band in the left middle frontal gyrus during EO, and it reduced power from 8.5 to 18.4 Hz in a brain area spanning from the superior frontal gyri to the supplementary motor areas during EC. In conclusion, the results suggest that nicotine counteracts the phenomenon of anteriorization of α activity, hence potentially increasing the level of vigilance.