Urinary epidermal growth factor/creatinine (EGF/Cr) excretion increases after prolonged therapy with 0.09 to 0.1 mg/kg bodyweight/week pituitary-derived growth hormone (GH) given 3 times weekly to GH-deficient children. We studied the short term and 1-month effects of 0.3 mg/kg/week of recombinant human growth hormone (rhGH) administered either daily (n = 12, 0.043 mg/kg/day) or 3 times weekly (n = 7, 0.1 mg/kg/day) on plasma and urinary EGF/Cr excretion in newly diagnosed GH-deficient children (all male, mean age 12.8 ± 3.3 years). Total 24-hour urinary EGF/Cr excretion was greater immediately after a single dose of rhGH 0.1 mg/kg compared with that after a single dose of 0.043 mg/kg (195.6 ± 27.4ng EGF/mg Crvs138.9 ± 10.2 ng/mg, respectively, p = 0.04). After 1 month, total 24-hour urinary EGF/Cr excretion of the daily group increased from 138.9 ± 10.2 ng/mg initially to 225.8 ± 38.8 ng/mg (p = 0.03), and was virtually identical to that of the 1-month 3-times-weekly 24-hour excretion (216.9 ± 38.7 ng/mg). During a 24-hour period, urinary EGF excretion varied with rhGH dose, time and duration of therapy. Plasma EGF concentrations did not change after 1 month of either daily (1.6 ± 0.1 ng/mlvs1.3 ± 0.2 pretreatment) or 3-times-weekly (1.3 ± 0.4 ng/mlvs1.1 ± 0.2 pretreatment) rhGH. We conclude that urinary EGF/Cr but not plasma EGF concentrations increase as a function of both rhGH dosage and duration of treatment in children with GH deficiency.