We determined the concentrations of immunoreactive epidermal growth factor (irEGF) and creatinine in urine samples from 47 adult patients with various kidney diseases and wide ranges of azotemia and proteinuria. In most of the patients, urinary irEGF concentrations (nanograms per mg creatinine) were markedly subnormal. In the entire group, urinary irEGF correlated with creatinine clearance (r = 0.79; P less than 0.001) and serum creatinine concentration (r = -0.85; P less than 0.001). In the subgroups of patients with primarily glomerular or tubulointerstitial diseases, similar correlations were found. By contrast, there was no correlation with proteinuria. We also determined the concentrations of plasma irEGF in five patients with azotemia. In four patients, the irEGF to creatinine concentration ratio was 1.9- to 8.9-fold higher in urine than in plasma, indicating that plasma irEGF was not the main source of urinary irEGF in these patients. Our data are compatible with the theory that urinary irEGF originates from nephrons per se.