The APPswe/PS1dE9 mouse is a double transgenic model of Alzheimer's disease, which harbors mutant mouse/human amyloid precursor protein (Swedish K594N/M595L) and presenilin-1 genes (PS1-dE9). These mice develop β-amyloid plaques and exhibit visuo-spatial learning and memory impairment in the Morris water maze (MWM) at 8–12 and 16–18 months of age. To extend these findings, we tested visuo-spatial learning and memory of male and female APPswe/PS1dE9 mice at 16 months of age on the Barnes maze. APPswe/PS1dE9 mice showed impaired acquisition learning using measures of latency, distance traveled, errors and hole deviation scores, and were less likely to use the spatial search strategy to locate the escape hole than wild-type mice. APPswe/PS1dE9 mice also showed a deficit in memory in probe tests on the Barnes maze relative to wild-type mice. Learning and memory deficits, however, were not found during reversal training and reversal probe tests. Sex differences were observed, as male APPswe/PS1dE9 mice had smaller reversal effects than male wild-type mice, but females of each genotype did not differ. Overall, these results replicate previous findings using the MWM, and indicate that APPswe/PS1dE9 mice have impaired visuo-spatial learning and memory at 16 months of age.