Whilst the content of epidermal growth factor in the submandibular salivary glands has been considered to be controlled primarily by the hormonal secretions of the testes, our previous studies indicated that the adrenal glands also affect the cellular content of epidermal growth factor in these glands. In the present study, the influence of the thyroid gland was investigated. One hundred and ten males Swiss White mice were subjected to orchidectomy and/or bilateral adrenalectomy, or thyroidectomy, and their submandibular salivary glands examined at 90 days of age. Some of these received specific hormone replacement prior to examination of the glands. The presence of epidermal growth factor was detected by indirect immunofluorescence, and adjacent sections of tissue were stained with alcian blue and acid fuchsin to demonstrate the convoluted granular tubules, which are the site of storage of the factor in the glands. In the glands of normal males, these tubules were prominent and showed strong factor-positive immunofluorescence. Administration of thyroxine reversed orchidectomy-induced atrophy of the tubules, and restored factor content, but did not restore normal tubular morphology or factor content in orchidectomised-adrenalectomised animals. In these latter animals, combined administration of thyroxine and cortisone resulted in a return to normal structure and growth factor content in the cells of the convoluted granular tubules. The glands from thyroidectomised males had atrophied tubules, which did not contain demonstrable epidermal growth factor. These effects were reversed by the administration of thyroxine, testosterone, thyroxine and testosterone, or thyroxine and cortisone. The results show that the content of epidermal growth factor-positive cells in the convoluted granular tubules of the submandibular salivary glands of male mice is under the control of the thyroid as well as the testes and adrenal glands.