Overt production of ASL signs was evaluated using H(2)(15)O PET to differentiate brain systems that support sign language production at the lexical-selection and phonological-articulatory levels. Subjects were 16 right-handed, congenitally deaf native ASL signers (10 women, six men; age 20 to 29 years). Scans were performed while subjects (1) passively viewed ASL nouns, (2) repeated nouns, (3) generated verbs in response to these nouns, (4) passively viewed videotaped segments depicting transitive actions, and (5) generated a verb to describe these actions. Conjunctions between the two verb-generation tasks revealed left-lateralized activation of perisylvian, frontal, and subcortical regions commonly observed in spoken language generation tasks and implicated in processes of semantic feature binding and lexical selection. Analysis of noun repetition minus viewing condition revealed activation of distinct systems supporting phonological encoding and articulation, including bilateral activation of sensorimotor areas and association cortices in the temporal, parietal, and occipital lobes. In addition, lexical-selection and articulatory processes were associated with activation of different corticostriatal-thalamocortical circuits: articulation with activation of the motor, and lexical-selection with activation of the prefrontal circuits, respectively. The results collectively provide insight into dissociable neural systems underlying these psycholinguistic functions. In addition, activation of regions that are typically associated with the auditory system during sign production suggests that these regions may support modality-independent linguistic processes, or may indicate cross-modal plasticity within the deaf brain.