Children with growth failure, normal growth hormone responses to stimulation tests, and low somatomedin levels are being recognized with increasing frequency. Sixteen patients, aged 2 to 17 years, with these findings were studied. When treated with human growth hormone, the mean plasma somatomedin-C levels of these patients increased from 0.19 +/- 0.05 (SD) U/mL to 2.29 +/- 1.11 U/mL (P less than .001) and mean growth velocity increased from 3.6 +/- 1.6 (SD) cm/yr to 7.4 +/- 2.9 cm/yr at 8 months of treatment (P less than .001). The effect of human growth hormone therapy on the whole group was statistically significant, but the effect on individuals was highly variable. There was no correlation between magnitude of the increase in somatomedin-C and growth response (r = .26, NS). Thus, the long-term growth-promoting effect of human growth hormone therapy in this group of patients could not be predicted from the magnitude of the somatomedin-C responses.