To examine the biological basis of subjective memory impairment (SMI), defined as the feeling of memory worsening with normal memory performance, we measured the volume of the entorhinal cortex (EC) and the hippocampus in SMI subjects, patients with mild cognitive impairment (MCI), patients with Alzheimer's disease (AD) and healthy controls (CO). Compared with controls, the EC was smaller in the SMI group (left: p=0.060; right: p=0.045) and in the other two groups in the following order: CO>SMI>MCI>AD. The same sequence was observed with regard to hippocampal volumes, but the volume reduction of the left hippocampus in the SMI group only reached a trend towards significance (p=0.072) and the right was not significantly smaller compared with controls (p=0.37). Compared with controls the average (left/right) volume reduction of the EC was 18% (SMI), 26% (MCI) and 44% (AD). The mean volume reduction of the hippocampus was 6% (SMI), 16% (MCI) and 19% (AD). Our results mirror the temporal sequence of neurodegeneration in AD and support the concept of SMI as the first clinical manifestation of dementia.