In patients with Alzheimer's disease (AD), postmortem and imaging studies have revealed early and prominent reductions in cerebral serotonin 2A (5-HT_2A) receptors. To establish if this was due to a selective disease process of the serotonin system, we investigated the cerebral 5-HT_2A receptor and the serotonin transporter binding, the latter as a measure of serotonergic projections and neurons. Twelve patients with AD (average Mini Mental State examination [MMSE]: 24) and 11 healthy age-matched subjects underwent positron emission tomography (PET) scanning with [¹⁸F] altanserin and [¹¹C] DASB. Volumes of interest were automatically delineated on coregistered magnetic resonance imaging (MRI) scans and the data were partial volume corrected. Overall [¹⁸F] altanserin binding was markedly reduced in AD by 28%–39% (p = 0.02), whereas the reductions in [¹¹C] DASB binding were less prominent and mostly insignificant, except for a marked reduction of 33% in mesial temporal cortex (p = 0.0005). No change in [¹¹C] DASB binding was found in the midbrain. We conclude that the prominent reduction in neocortical 5-HT_2A receptor binding in early AD is not caused by a primary loss of serotonergic neurons or their projections.