In the management of head and neck tumors by radiotherapy, the patients are prone to suffer from radiation-induced damage of the salivary glands. This experiment was carried out to examine the effect of pilocarpine and atropine on the rat submandibular gland and to establish whether it is possible to protect the salivary glands from irradiation by altering the amount of secretory granules in the serous cells prior to irradiation. The submandibular glands of rats were irradiated after pretreatment with or without drugs. Single irradiation of 18 Gy caused significant damage to the submandibular glands without pretreatment, showing the most severe changes 1 week after irradiation and slowly recovering thereafter. Pilocarpine pretreatment was protective against irradiation, displaying much less damage after irradiation of the same dosage, and with complete recovery after 4 weeks. On the other hand, atropine-pretreated animals revealed more extensive damage than the other two groups, possibly due to the retention of secretory granules.