Indirect speech acts—responding “I forgot to wear my watch today” to someone who asked for the time—are ubiquitous in daily conversation, but are understudied in current neurobiological models of language. To comprehend an indirect speech act like this one, listeners must not only decode the lexical-semantic content of the utterance, but also make a pragmatic, bridging inference. This inference allows listeners to derive the speaker’s true, intended meaning—in the above dialog, for example, that the speaker cannot provide the time. In (...) the present work, we address this major gap by asking non-aphasic patients with behavioral variant frontotemporal dementia and brain-damaged controls with amnestic mild cognitive impairment to judge simple question-answer dialogs of the form: “Do you want some cake for dessert?” “I’m on a very strict diet right now,” and relate the results to structural and diffusion MRI. Accuracy and reaction time results demonstrate that subjects with bvFTD, but not MCI, are selectively impaired in indirect relative to direct speech act comprehension, due in part to their social and executive limitations, and performance is related to caregivers’ judgment of communication efficacy. MRI imaging associates the observed impairment in bvFTD to cortical thinning not only in traditional language-associated regions, but also in fronto-parietal regions implicated in social and executive cerebral networks. Finally, diffusion tensor imaging analyses implicate white matter tracts in both dorsal and ventral projection streams, including superior longitudinal fasciculus, frontal aslant, and uncinate fasciculus. These results have strong implications for updated neurobiological models of language, and emphasize a core, language-mediated social disorder in patients with bvFTD. (shrink)