Growth deficiency is a cardinal feature of severe osteogenesis imperfecta (OI) and a frequent feature of mild to moderate forms of this disease. We have investigated the status of hormones related to growth in 22 short prepubertal children, 13 males and 9 females, with various types of OI. Ten children had Sillence type III OI, 10 had type IV, and 2 had type I. Evaluation included GRH stimulation, three standard GH provocative tests (arginine-insulin tolerance test, L-dopa), 24-h sampling for measurement of unstimulated GH secretion and a somatomedin-C generation test. None of these children had GH deficiency by standard criteria. We found that 9 OI children had decreased responsiveness to GRH, similar to the GRH response of GH-deficient children. Overall, however, mean 24-h GH values and mean peak GH response to provocative agents of OI children were within the normal range. In the somatomedin generation test, the OI children as a group showed a blunted response, with 13 of 22 having less than a 2-fold stimulation of somatomedin-C by GH. This suggested resistance of the liver and other somatomedin-C secreting tissues to GH. The group with blunted insulin-like growth factor-I response did not correlate significantly with the group with decreased GRH response. To investigate the responsiveness of OI bone to growth stimulation, six OI children with less than average integrated GH secretion were enrolled in a pilot study in which one child received exogenous GH and six received clonidine for at least 6 months. The child treated with exogenous GH and three of six treated with clonidine experienced at least a 4.7 cm/yr increase over their pretreatment growth rates. Growth response could not be predicted from baseline studies. We conclude that abnormalities of the GH-somatomedin axis exist in some children with OI. Administration of GH or clonidine may augment growth rates in OI children; however, the effect of these agents on final stature is unknown.