Many thyroid carcinomas seem to be dependent upon the thyroid growth-promoting properties of the thyroid stimulating hormone (TSH). The purpose of the present investigation was to compare the in vitro effect of TSH on tissue cultures derived from malignant and benign thyroid tumors. The results indicate that TSH can affect the morphology and protein synthesis of primary tissue cultures derived from benign and malignant thyroid tumors differently. The addition of TSH to cultures derived from benign tumors resulted in a reorganization of follicle-like structures of the monolayer and in a reduction of protein synthesis. In contrast to this, monolayers derived from carcinomas of the thyroid were not able to reorganize and their protein synthesis was not inhibited in the presence of TSH. For a better understanding of TSH suppressive therapy, we suggest testing the influence of TSH on a large number of tissue cultures derived from benign and malignant tumors of the thyroid.