The Tg2576 Alzheimer's disease (AD) mouse line shows a marked increase in amyloid-b (Ab) 1–40 and Ab1–42 in the plasma and brain by 3–5 months of age, decrease in spine density in the dentate gyrus at 4 months, decline in long-term potentiation of synaptic transmission in the dentate gyrus associated with impairment in contextual fear conditioning by 5 months, and plaque deposition in brain starting at 8 months. Visual recognition memory is seriously impaired in patients in the early stages of AD. The perirhinal cortex (Prh), a multimodal associative cortex of the temporal lobe, is critically involved in this form of memory; long-term depression of synaptic transmission (LTD) in this cortical region is regarded as its cellular correlate. The present work was aimed at evaluating if LTD in Prh of Tg2576 mice is already compromised at 3 months of age. Field excitatory post-synaptic potentials evoked by afferent pathways stimulation were recorded in layer II/III of Prh in horizontal brain slices obtained from 3 month old Tg2576 mice and littermate controls. We found that a single train of 3000 pulses delivered at 5 Hz induced LTD in slices from control mice, but not in those from Tg2576 mice. This result is consistent with the early visual recognition impairment observed in AD patients, and is particularly interesting because no changes in synaptic plasticity have previously been found so early in this transgenic line.