We have attempted to evaluate the relationship between spontaneous growth hormone (GH) secretion and the response to GH therapy as well as the effect of discontinuation of GH therapy on further growth. The 24-h integrated concentration of GH (ICGH) was determined in 150 short children (< 2 SD for age) with a GH response to clonidine stimulation of more than 10 mcg/L. The patients were treated with GH for 4 yr and were observed for 1 yr following cessation of GH treatment. Twenty-two out of 52 patients who had an ICGH of less than 3.2 mcg/L (group LICGH) and 28 out of 60 patients who had an ICGH of more than 3.2 mcg/L (group NICGH) were followed without GH therapy. Only patients who remained prepubertal throughout the study were included in the analysis. The growth response of the LICGH to GH was better than that of the NICGH children. Patients regained normal growth velocity 6-12 months after discontinuation of GH therapy. Three children of the LICGH subsequently developed classic GH deficiency. These studies demonstrate that short-term GH therapy can improve the growth channel. Children with a low ICGH grow better on GH than children with a normal ICGH. Children with a low ICGH need continued observation and retesting when growth velocity is low.