Studies in macaque monkeys indicate that the perirhinal cortex in the temporal lobe participates in object memory. This function may be analogous to aspects of human semantic memory (knowledge of objects, concepts, faces and words). To date, the status of perirhinal cortex has not specifically been investigated in patients with semantic deficits as seen in semantic dementia, the temporal lobe variant of frontotemporal dementia. High-resolution three-dimensional magnetic resonance imaging was performed in subjects with semantic dementia and Alzheimer's disease (characterized in its early stages by selective episodic memory impairment) and in healthy age-matched controls. Hippocampal, perirhinal, temporopolar and entorhinal cortex volumes were measured by outlining areas on successive scan slices according to recognized landmarks. The entorhinal and hippocampal regions were further subdivided into anterior and posterior parts. In keeping with the hypothesized contribution of the perirhinal cortex to semantic memory function, we found greater involvement of this region, together with the temporopolar and anterior entorhinal cortices, in semantic dementia than in either Alzheimer's disease patients or control subjects. Performance on a range of semantic tests also correlated with perirhinal volume. Bilateral reduction in hippocampal volume compared with controls was seen in Alzheimer's disease. In conclusion, atrophy of the human perirhinal cortex, and of directly connected areas, was associated with semantic memory impairment but not episodic memory impairment, as predicted from the primate work.