A PET activation study was designed to investigate hemispheric specialization during speech comprehension and production in right- and left-handed subjects. Normalized regional cerebral blood flow (NrCBF) was repeatedly monitored while subjects either listened to factual stories (Story) or covertly generated verbs semantically related to heard nouns (Gener), using silent resting (Rest) as a common control condition. NrCBF variations in each task, as compared to Rest, as well as functional asymmetry indices (FAI = right minus left NrCBF variations), were computed in anatomical regions of interest (AROIs) defined on the single-subject MNI template. FAIs were predominantly leftward in all regions during both tasks, although larger FAIs were observed during Gener. Subjects were declared "typical" for language hemispheric specialization based on the presence of significant leftward asymmetries (FAI < 0) in the pars triangularis and opercularis of the inferior frontal gyrus during Gener, and in the middle and inferior temporal AROIs during Story. Six subjects (including five LH) showed an atypical language representation. Among them, one presented a right hemisphere specialization during both tasks, another a shift in hemispheric specialization from production to comprehension (left during Gener, right during Story). The group of 14 typical subjects showed significant positive correlation between homologous left and right AROIs NrCBF variations in temporal areas during Story, and in temporal and inferior frontal areas during Gener, almost all regions presenting a leftward FAI. Such correlations were also present in deactivated areas with strong leftward asymmetry (supramarginalis gyrus, inferior parietal region). These results suggest that entry into a language task translates into a hemispheric reconfiguration of lateral cortical areas with global NrCBF increase in the dominant hemisphere and decrease in the minor hemisphere. This can be considered as the setting up of a "language mode", under the control of a mechanism that operates at a perisylvian level. On top of this global organization, regional variations carry on the performance of the cognitive operations specific to the language task to be performed. Hemispheric relationships could be different in atypical subjects, with either between task hemispheric regulation differences or differences in regional specialization.