The purpose of this study was to compare the language and cognitive profiles of four progressive nonfluent aphasia (PNFA) patients with 25 probable Alzheimer's disease (pAD) patients, and to identify the distinct cortical defects associated with cognitive deficits in PNFA using positron emission tomography (PET). Longitudinal observations of PNFA patients revealed progressively telegraphic speech and writing and a gradual deterioration of sentence comprehension, but memory and visual functioning were relatively preserved. Direct contrast with PAD patients revealed that PNFA patients are significantly impaired on grammatical phrase structure aspects of sentence comprehension and expression, phonemic judgments, repetition, and digit span, but not on other cognitive measures. PET studies of PNFA revealed reduced cortical activity throughout the left hemisphere. In addition, there was a prominent defect in left superior and middle temporal and inferior frontal regions of PNFA patients that differed significantly from the distribution of regional cerebral dysfunction in pAD. We conclude that PNFA is associated with a distinct profile of language and cognitive difficulty, and that this pattern of impairment is related to cortical dysfunction in a specific distribution of the left hemisphere.