Type IV collagen production by cultured rat glomerular mesangial cells was evaluated quantitatively by measuring type IV collagen secreted into culture media and associated with the cells using enzyme-linked immunosorbent assay (ELISA). The majority of type IV collagen was secreted into culture media; type IV collagen increased with cell growth in the early log phase and decreased in the late log phase and after cofluency. By exposing the cells to high concentrations of glucose (27.8 mM), both secreted and cell-associated type IV collagens increased significantly compared with the cells cultured under normal glucose concentrations (5.6 mM) or under equivalent concentrations of mannitol, resulting in a significant increase in total type IV collagen accumulation.