Poor prognosis and limited therapeutic options characterize immunoglobulin light chain (AL) amyloidosis with major heart involvement. Reliable experimental models are needed to study light chains (LC)-heart interactions and to explore strategies for prevention of cardiac damage. We have exploited the nematode C. elegans as a novel tool, since its pharynx is evolutionarily related to the vertebrate heart. Our data demonstrate that the pharyngeal pumping of C. elegans is significantly and selectively reduced by LC from AL patients suffering from cardiomyopathy, but not by amyloid LC with different organ tropism or non-amyloidogenic LC from multiple myeloma. This functional alteration is dependent on the LC concentration and results in persistent pharyngeal dysfunction and in a significant reduction of the worms' lifespan. These manifestations are paralleled by an increase of mitochondrial reactive oxygen species and can be prevented by treatment with antioxidant agents. In conclusion, these data indicate that this nematode-based assay is a promising surrogate model for investigating the heart-specific toxicity of amyloidogenic LC and for a rapid screening of new therapeutic strategies.