The aim of this study was to analyze the timing and topography of brain activity in relation to the cognitive processing of different types of auditory information. We specifically investigated the effects of familiarity on environmental sound identification, an issue which has been little studied with respect to cognitive processes, neural substrates, and time course of brain activity. To address this issue, we implemented and applied an electroencephalographic mapping method named event-related desynchronization, which allows one to assess the dynamics of neuronal activity with high temporal resolution (here, 125 ms); we used 19 recording electrodes with standard positioning. We designed an activation paradigm in which healthy subjects were asked to discriminate binaurally heard sounds belonging to one of two distinct categories, "familiar" (i.e., natural environmental sounds) or "unfamiliar" (i.e., altered environmental sounds). The sounds were selected according to strict preexperimental tests so that the former should engage greater semantic, and the latter greater structural, analysis, which we predicted to preferentially implicate left posterior and right brain regions, respectively. During the stimulations, significant desynchronizations (thought to reflect neuronal activations) were recorded over left hemisphere regions for familiar sounds and right temporofrontal regions for unfamiliar sounds, but with only few significant differences between the two sound categories and a common bilateral activation in the frontal regions. However, strongly significant differences between familiar and unfamiliar sounds occurred near the end of and following the stimulations, due to synchronizations (though to reflect deactivations) which appeared over the left posterior regions, as well as the vertex and bilateral frontal cortex, only after unfamiliar sounds. These unexpected synchronizations after the unfamiliar stimuli may reflect an awareness of the unfamiliarity of such sounds, which may have induced an inhibition of semantic and episodic representations because the latter could not be associated with meaningless sounds.