Idiopathic growth hormone (GH) deficiency is a clinically and biologically heterogeneous condition. This study evaluates the capacity of the initial growth response to hGH therapy to distinguish certain from transient GH deficiency. Twenty-five patients having a GH peak < 10 micrograms/l after 2 pharmacological stimulation tests were classified according to the accuracy of the diagnosis of GH deficiency. Group 1 (n = 17) had certain GH deficiency because of pituitary stalk interruption syndrome and/or familial form. Group 2 (n = 8) had a transient GH deficiency. The mean increase in height standard deviation (SD) was 1.3 +/- 0.1 (mean +/- SE) and 0.5 +/- 0.1 during the first and second years in group 1 and 0.4 +/- 0.1 (p < 0.0005, compared to group 1) and 0.1 +/- 0.2 (p < 0.025 compared to group 1) during the first and second years in group 2. During the first year of therapy, the increase in height was > or = 1 SD in 14 patients of group 1 and in 1 patient of group 2. In group 1, this increase was positively correlated with an increase in body mass index (r = 0.80, p < 0.01) during the first year and with target height (r = 0.60, p < 0.02) during the second year. Growth rate (SD for age) during the first year in this group was negatively correlated with the height prior to therapy (r = -0.72, p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)