The serum levels of immunoreactive somatomedin A (SMA) in 23 patients with Cushing's disease, aged 6-61 years, were within the range of healthy subjects for their ages. No correlation was found between SMA and the excretion of cortisol. After im administration of hGH (8 IU = 4 mg) daily for 3 days there was a significant rise in SMA, both determined by radioimmunoassay and radioreceptor assay. Thus no impairment was found in the GH-dependent SMA levels or the ability of hGH to generate somatomedin, which indicates that the growth retarding effect of cortisol is most likely due to a direct effect on the tissue. After treatment with stereotactic radiation to the hypophysis there was a significant decrease in cortisol excretion without any change in SMA levels, indicating the possibility to achieve a selective impairment of the ACTH-cortisol axis.