To obtain more information about a possible role of somatomedins in mediating the effects of thyroid hormones on the development and function of epiphyseal cartilage, somatomedin activity, measured on the basis of 35S incorporation in embryonic chick cartilage, was studied in thyrotoxic patients before and after treatment with carbimazole or surgery and in a group of patients with primary hypothyroidism. In 29 hyperthyroid patients mean values of somatomedin were 1.29 .+-. 0.03 standard error of the mean and differed significantly (P < 0.01) from normals (1.04 .+-. 0.03). In 15 carbimazole treated patients and in 5 operated patients with thyrotoxicosis somatomedin levels fell from 1.29 .+-. 0.04 to 1.03 .+-. 0.04 (P < 0.01) when the patients became euthyroid. Correspondingly, somatomedin levels in 12 untreated hypothyroid patients (0.82 .+-. 0.04) were significantly less than in normals (P < 0.01) and increased from 0.77 .+-. 0.09 to 1.14 .+-. 0.13 (P < 0.05) in 4 patients on replacement therapy. Somatomedin levels rise when thyroid hormones are present in excess, and fall when these are deficient. Thyroid hormones apparently are important regulators of somatomedin levels.