Hyperphagia and associated eating changes occur frequently in Alzheimer's disease (AD) and lead to considerable morbidity. However, the neurochemical basis for these neuropsychiatric behaviours is at present unclear. In this study, we measured serotonin transporters, 5-HT(1A), 5-HT(2A), and 5-HT(4) receptors using radioligand binding assays in the postmortem temporal cortex of a cohort of controls and AD patients longitudinally assessed for hyperphagia. We found significant decreases in 5-HT(4) receptor densities in the hyperphagic, but not normophagic, AD group. Our data suggest that 5-HT(4) receptor deficits may be a specific neurochemical correlate of hyperphagia, and point to the potential pharmacotherapeutic utility of 5-HT(4) agonists for these behaviours in AD.