The cast-engulfing giant cells in a case of kappa light chain nephropathy/Bence Jones cast nephropathy were characterized with monoclonal antibodies Uro-5 (renal epithelium: Henle's loop, distal tubule, collecting duct) and Leu-M5 (macrophage/monocyte/dendritic cell specific). The giant cells were Leu-M5 positive and Uro-5 negative. There was an increased concentration of Leu-M5-positive cells surrounding cast-containing tubules, and occasional Leu-M5-positive cells were found within the tubular epithelial layer. Although there were no Uro-5-positive giant cells, an occasional Uro-5-positive cell was found within casts. The majority of casts were found within Uro-5-positive tubules. These results confirm earlier electron microscopic reports that the cell of origin of the cast-engulfing multinucleated giant cell is the macrophage (Leu-M5 positive, Uro-5 negative). These giant cells may originate from macrophages that have migrated from the interstitium through the tubular epithelium.