FOCAL deposits of beta-amyloid (βA) in the hippocampus have been implicated in Alzheimer's disease. In this study we assessed the effects of bilateral injections into the hippocampus of βA(25–35), a combination of βA(25–35) with ibotenic acid (IBO), and IBO on spatial learning in the rat. Bilateral injections of βA(25–35) into the hippocampus together with IBO (which by itself has no neurotoxic effects) produced a dramatic disruption in the acquisition of a spatial learning in the rat. Separate injections into the hippocampus of βA(25–35) or the incubated form of βA(25–35) alone failed to significantly affect maze acquisition in the rat. Histological examination revealed that only the combination of βA(25–35) with IBO produced a lesion along with focal deposits in the hippocampus.