There is controversy over the origin of cells in glomerular crescents. Although crescent cells were once considered to be of epithelial lineage, recent data have suggested that they are derived from the mononuclear phagocyte system. To further define the histogenesis of crescents, the authors evaluated 26 renal biopsy specimens having cellular crescents, using immunoenzyme and immunofluorescence microscopy, and a battery of 11 antibodies reactive with renal epithelial cells and 5 antibodies reactive with leukocytes. Although minor populations of macrophages were present in most crescents, in only 1 of 23 specimens evaluated with anti-macrophage antibodies were these the major cell type. Of 23 specimens evaluated with anti-epithelial antibodies, all but one had crescents with most of the cells expressing one or more epithelial antigens. Crescent cells shared antigens with glomerular and tubular epithelial cells, but the antigen phenotype of crescents often differed from that of normal tubular or glomerular epithelial cells.