Two patients with nonfluent progressive aphasia, who have been studied longitudinally, are contrasted with a group of 5 patients with fluent progressive aphasia or semantic dementia. The most prominent feature of the nonfluent syndrome is the severe distortion of speech output with phonological errors and agrammatic sentence structure. This contrasts with the fluent, well articulated and syntactically correct, but empty, anomic speech found in semantic dementia. Performance on tests of comprehension separates the patient groups: The nonfluent patients show normal single-word comprehension, but marked impairment on tests of syntactic comprehension, while those with semantic dementia demonstrate the opposite pattern. Category fluency is severely defective in semantic dementia, but initial letter-based fluency is more impaired in the nonfluent syndrome. Performance on nonverbally mediated tests of semantic knowledge is impaired in semantic dementia only. The 2 forms of progressive aphasia have in common the sparing of perceptual and visuospatial skills, nonverbal problem solving abilities, and day-to-day (episodic) memory. Neuroradiological investigations have shown marked selective and striking inferolateral left temporal lobe atrophy in all 5 patients with semantic dementia. The changes in nonfluent progressive aphasia appear to be less focal and involve left perisylvian structures more diffusely. These 2 forms of progressive aphasia are, we argue, distinct in their manifestations.