A 17 year-old female with septo-optic dysplasia (SOD) and hypopituitarism who has grown normally despite GH deficiency is presented. Her serum was examined to test current hypotheses to explain the phenomenon of growth without GH. The patient's serum possessed potent in vitro growth- promoting activity (GPA) in an erythroid progenitor-cell clonal proliferation assay consistent with the patient's normal growth performance. In contrast to previously reported cases of growth without GH, total IGF-I concentrations were very low in this patient, precluding IGF-I being responsible for the observed GPA and normal growth pattern. Furthermore, circulating free IGF-I was also low which is reported for the first time in such a case. A detailed picture of IGF-binding proteins is also presented. To test the hypothesis that hyperinsulinemia might be responsible for the observed GPA, in vitro GPA experiments were performed before and after removal of insulin by immunodepletion. Neither partial nor complete removal of insulin abolished the in vitro cell proliferation response. These data demonstrate that neither IGF-I nor insulin is the factor responsible for GPA in at least this patient with SOD and growth without GH.