Objectives We explored the underlying mechanisms that facilitate reducing and enhancing effects of exogenous proteins on cytotoxicity of amyloid beta (A beta), a main pathogen of Alzheimer's disease, by using anEscherichia colichaperonin DnaK. Results DnaK was chosen as a tool, because it, easily available and functionally stable, reduced or enhanced A beta cytotoxicity depending on its concentration. Cytotoxicity was enhanced when the molar ratio of DnaK to A beta 42, at 20 mu M A beta 42, was 0.01-0.5, while reduced cytotoxicity was observed at higher ratios (> 1) at 1 mu M A beta 42. Significant amounts of oligomeric A beta 42 species accumulated concomitantly with enhanced cytotoxicity, whereas the oligomers appeared to form complexes with DnaK in conditions of reduced cytotoxicity. Conclusions The difference in cytotoxicity was due to variations in the toxic oligomeric A beta species and DnaK is a useful tool for the study of the A beta ultrastructure formation and toxicity of A beta peptide.