The pathological features of Alzheimer's disease include deposition of amyloid-β (Aβ) containing plaques and increases in the expression of cyclin-dependent kinase (CDK) enzymes. Chemical inhibition of CDKs prevents the neurotoxicity of the Aβ peptide. The activity of these kinases requires the binding of a cyclin component to the catalytic enzyme component. This study characterizes direct interactions between Aβ and cyclin B1. Aβ fragments containing the cytotoxic 31–35 region could inhibit biotinylated Aβ binding to cyclin B1. The same cytotoxic Aβ fragments all increased CDK-1 phosphorylation of known substrates in a cell free system. The CDK-1 inhibitor olomoucine prevented the cytotoxicity of Aβ 31–35 containing peptides in differentiated human teratocarcinoma cell line, Ntera 2/cl-D1 (NT-2) neurons. These direct interactions between cyclin B1 and Aβ provide potential mechanisms for the cytotoxicity of the Aβ peptide.