The histogenesis of the multinucleated cells that characterize myeloma cast nephropathy ("myeloma kidney") has long been a subject of debate. Recent studies have implicated monocyte/macrophage-derived cells rather than tubular epithelial cells as the progenitors of these multinucleated cells. In this study a panel of antibodies including one with high specificity for macrophages was used to study four cases of myeloma cast nephropathy. The authors' findings extend previous observations of others to confirm the macrophage origin of the multinucleated cells in this form of renal injury.