Four prepuberal children, two girls and two boys, aged 7 years 3 months to 11 years 6 months with chronic growth retardation were studied. Informed parental consent was obtained. Growth was followed for two years or more and was always less than P 3. Growth velocity during observation period was 4 cm/y or less. Gastrointestinal, hepatic, renal and thyroid functions were normal. Skeletal X-ray examination revealed no anomalies. karyotype in the two girls was 44XX. Growth hormone (GH) secretion was evaluated in all cases by two different test: exercise-propranolol and insulin-induced hypoglycemia. Peaks of GH secretion were 10 ng/ml or more. In three patients, GH secretion was also evaluated during first two hours of deep-sleep. GH peaks were 10, 4 and 13.4 ng/ml, respectively. Somatomedin activity (SA) measured in basal condition on two different days with six month interval was low (0.28-0.70 U/ml) and increased after seven daily doses of 2 mg of GH, in all patients (0.80-1.12 U/ml). All patients were treated with GH (2 mg/3 times/week), and growth velocity increased from 4 to 8.7, from 3.9 to 8.8, from 3 to 6.5 and from 3.2 to 6 cm/y, respectively. In conclusion, SA is of value in selection of patients with chronic growth retardation, who may benefit from long-term GH therapy.