Patients with probable Alzheimer's disease are thought to have a semantic memory deficit. We used functional MRI to evaluate the neural basis for impaired semantic memory for ANIMALS and IMPLEMENTS in 11 patients with Alzheimer's disease and 16 healthy seniors. For both categories of knowledge, Alzheimer's disease patients show reduced activation in the left posterolateral temporal-inferior parietal cortex compared with healthy seniors. Activation changes in this heteromodal association region may be related to an impairment of the category-neutral semantic processes involved in integrating feature knowledge that is represented in modality-specific association cortices. We also found increased activation of an area of the left temporal cortex for both categories of knowledge in Alzheimer's disease that was not activated in healthy seniors. Category-specific changes were also seen in Alzheimer's disease compared with healthy seniors that may be related to the neural representation of category-specific feature knowledge represented in semantic memory. For ANIMALS, the left ventral temporal cortex was activated in Alzheimer's disease in an anatomical distribution that was posterior to the left ventral recruitment for this category in healthy seniors. For IMPLEMENTS, frontal-striatal regions were activated in Alzheimer's disease in a manner that was displaced from the locus of recruitment for this category in healthy seniors. Our findings are consistent with a two-component model of semantic memory involving category-neutral processes operating on category- specific knowledge, and both components appear to be compromised in Alzheimer's disease. Components of the large-scale neural network underlying semantic memory may modify themselves to maintain performance in the face of a neurodegenerative disease.