Alzheimer's β-amyloid peptide (βAP) is known to possess a wide range of toxic effects on neurons in vitro and in vivo; however, there is little information available regarding its impact on other excitable tissues such as skeletal muscles, which, apart from brain cells, are thought to also be targets of βAP. Utilizing the combination of electrophysiology and myography, we investigated whether βAP also impairs the functioning of myocytes in frogs and mice. Although application of βAP in the range of 10(-6) to 10(-8) M induced depolarization of muscle fibers in both species, it impaired contractility in frogs but not in mice, by reducing endplate potential amplitude and increasing the threshold potential. Unchanged contractility in the mouse in the presence of βAP is due to a higher safety factor of neuromuscular transmission in mammals compared with amphibians. Possible clinical implications are discussed.