The major portion of circulating somatomedin (SM) is specifically carried by a large molecular weight binding protein of 150,000 (150K BP). There also exists a species of unsaturated binding protein in plasma of 40,000 mol wt that binds radiolabeled SM more avidly than the 150K complex. Patients with GH deficiency appear to have higher levels of this smaller BP while exhibiting decreased tracer binding and endogenous SM in the region of the 150K BP when compared to normals. This suggests the GH dependence of the 150K BP. We report studies on four GH-deficient children who had normal growth and normal SM levels after intracranial surgery. All were hyperphagic and obese at the time of study and were on replacement medications with the exception of GH. Endocrine evaluation revealed mild hyperprolactinemia in three patients and high insulin levels in three. SM-C/insulin-like growth factor I (IGF-I) levels by RIA and IGF-II by radioreceptor assay were normal for age. Sephacryl-200 column chromatography on plasma samples from these patients revealed patterns of tracer binding and endogenous SM migration similar to those of normal and GH-treated hypopituitary patients. The chromatograms were different from those usually seen in untreated GH-deficient patients. SM binding in whole serum was also similar to that observed in normal children (38 +/- 7% [125I]IGF-II bound for patients compared to 39 +/- 3% for controls) and less than that observed in GH-deficient children (48 +/- 5%). These data suggest that the characteristics of SM binding in our patients are similar to those of normal subjects. The regulation of the 150K BP is not accomplished by GH in these patients, although the exact mechanism for the maintenance of serum SM is unclear.