Considerable disagreement exists about the neuroanatomical basis of conceptual-semantic impairments observed in a subgroup of patients with Alzheimer's disease (AD) at mild to moderate stages of the disease. Several studies of groups of patients have shown correlations between focal hypometabolism or hypoperfusion in left hemispheric areas and measures of verbal semantic memory impairment in AD patients. The question remains, however, whether left hemispheric hypometabolism is sufficient to produce such impairment in the single case and whether nonverbal semantic knowledge is also affected. We used positron emission tomography (PET) with fluorodeoxyglucose-F18 (FDG), statistical parametric mapping (SPM), and tests of verbal and nonverbal semantic memory in 11 AD patients with a mean score on the Mini-Mental State Examination of 22.6 (+/-2.8). Naming impairment was significantly associated with left hemispheric asymmetry of hypometabolism on a single-case basis. Our correlation analysis showed that metabolism in left anterior temporal, posterior inferior temporal, inferior parietal and medial occipital areas (Brodmann areas: 21/38, 37, 40 and 19) correlated with both verbal and nonverbal semantic performance. We conclude that left hemispheric synaptic dysfunction, as measured by regional glucose hypometabolism, was sufficient to produce semantic impairments in our patients. The majority of areas affected in our patients with semantic impairments were involved in multimodal or supramodal (verbal and nonverbal) semantic knowledge.