In an attempt to elucidate the in vivo process of protein aggregation and mechanisms of amyloid organ disease, we have engineered a genetically defined mouse model of AL amyloidosis. These transgenic mice broadly expressing a human amyloidogenic lambda 6 immunoglobulin light chain (LC) using a cytomegalovirus (CMV) promoter have circulating LC and develop typical Congo red-positive amyloid deposits in the stomach, previously described at the XIth International Symposium on Amyloidosis in Woods Hole [1]. The CMV-lambda 6 transgenic mice display neurologic and metabolic phenotypes. The transgenic mice are larger and have metabolic dysregulation, accompanied by a decreased respiratory exchange ratio, indicating preferential lipid oxidation. With age, the mice develop hyperglycemia upon glucose challenge. We hypothesize that this may be due to a non-fibril-dependent effect of overexpression of LC in tissues, perhaps pancreas.