Somatomedin is the serum component which mediates growth hormone action on cartilage and other target tissues. This laboratory is engaged in the isolation and characterization of the somatomedin from the serum of acromegalic rats. We have adopted the system of extraction of Ginzberg et al which employs diafiltration through Amicon hollow fibers. Somatomedin is freed from its binding protein at pH 2.8 and passed through a 50,000 dalton exclusion hollow fiber. The somatomedin is subsequently concentrated by retention by a 5000 dalton exclusion hollow fiber. Subsequent purification has been with narrow range isoelectric focusing pH 8.0 to 9.5 and gel filtration through Sephadex G-50 superfine. A highly purified somatomedin is obtained by this procedure which will be characterized and its amino acid structure determined. This somatomedin preparation will also be utilized in radioreceptor and radioimmunoassay. Somatomedin receptors in fibroblasts and mononuclear cells of the peripheral blood of human beings will be studied to develop ways of comparing somatomedin binding by these receptors in hereditary conditions characterized by abnormal growth. Bioassay and radioreceptor assays of somatomedin are being conducted in various clinical conditions associated with normal circulating growth hormone and greatly retarded growth. We have recognized several patients with extremely low somatomedin levels in serum despite normal levels of growth hormone. These patients have responded to exogenous growth hormone with a rise to normal of serum somatomedin and when GH has been continued in 2 patients normal growth velocities have been restored. The nature of the growth impairment in these children is under continued study.