The degranulation and regranulation process was investigated after alpha-adrenergic stimulation on the rat submandibular gland. The submandibular gland in rat contains both serous and mucous cells. It has earlier been shown that serous cells filled with heavy-metal granules, are markedly more radiosensitive than cells without granules. In experiments with emptying the serous cell of their content of granules by administering an alpha-adrenergic stimulant, cyclocytidine, there has been found a decrease in irradiation damage in salivary gland tissue after irradiation. Injection of cyclocytidine, 150 mg/kg, was given i.p. to the rat. After 1 h there was almost complete depletion of granules in the serous cells, no morphological aberration was seen in the mucous cells. This effect still remained after 6 h. A beginning of regranulation with apical granules was seen 12 h after injection. After 24 h an almost complete regranulation had occurred in the salivary gland serous cells. The mucous cells did not show any morphological aberration. Our intent is to reduce unwanted salivary gland damage in patients with head and neck cancer when treated with radiotherapy. Depletion of heavy-metal granules in serous cells, before irradiation may diminish morphological destruction in the salivary glands. As a nearly total degranulation is present between 1-6 h after stimulation, this should be the optimal time for radiotherapy.