To investigate the excretion of urinary epidermal growth factor (EGF) in children with chronic renal failure (CRF), we have measured the urinary EGF/creatinine ratio (EGF/Cr) and the 24-hour urine EGF concentration in 19 children with CRF, 11 children with kidney disease and normal creatinine clearance, and 12 healthy children. Children with CRF had a significantly lower daily urine EGF concentration as well as urinary EGF/Cr. In contrast, children with kidney disease and normal renal function had normal daily urine EGF levels and urinary EGF/Cr. Accompanied by no difference in serum EGF between these two groups of patients, these data provide indirect evidence of the kidney as a source of human urinary EGF. There was a positive correlation of urinary EGF/Cr with creatinine clearance in all renal patients (r = 0.608, n = 30, p < 0.001). A much better correlation was found between daily urine EGF and creatinine clearance (r = 0.855, n = 30, p < 0.001). Our results implicate that there is a functional relationship between glomerular filtration and urinary EGF excretion, and that the urinary EGF/Cr may be a reliable indicator of urinary EGF excretion in children with CRF.