The gross, microscopic and ultrastructural lesions associated with the genetic disease, protoporphyria, in Limousin cattle were studied in detail. The clinical signs and lesions were most severe in young animals. In the liver, the lesions consisted of portal fibroplasia, bile ductule hyperplasia, parenchymal cell swelling, and pigment accumulation. Maltese cross-like crystals were evident under polarized light. Ultrastructurally, there were large secondary lysosomes comprised of electron-dense granules associated with lipid droplets in hepatocytes. Phagocytic cells in the dermis also contained large heterogeneous secondary lysosomes.