Radioimmunoassay for epidermal growth factor (EGF) was performed using the homogenates of glomeruli and tubular preparations obtained from normal human kidneys. EGF-immunoreactive material was 3- to 5-fold higher in the glomerular fractions than in the tubular fraction. By indirect immunofluorescence with a monoclonal antibody, EGF was positive in three of five normal human kidney tissues and in tissues of 24 of 33 patients with proliferative and nonproliferative types of glomerular diseases. Acid-urea treatment of tissue sections to unmask a hidden epitope of the EGF molecule disclosed EGF immunoreactivity in four more kidney specimens. EGF was localized along the glomerular capillary walls and was also present in the arterioles and small arteries. Staining with three monoclonal antibodies recognizing two different epitopes of EGF receptor (EGF-R) was positive in tissues of 2 normal subjects and 15 patients with glomerular diseases. EGF-R was found along the glomerular capillary walls, in peritubular capillaries, and within the epithelial cells of distal tubules and collecting ducts. Immunoelectron microscopy with colloidal gold staining showed that EGF and EGF-R were localized in the plasma membrane of glomerular endothelial cells. Immunofluorescence with or without acid-urea denaturation showed coexpression of EGF and EGF-R in glomeruli of 1 normal subject and 12 patients. This study demonstrated the presence of EGF and EGF-R in human glomeruli. There was no obvious difference in EGF and EGF-R expression in glomeruli derived from normal or diseased state.