A study has been made of the salivary glands of the rat following an injection of a sublethal dose of actinomycin D. Body weights and weights of the parotid and submandibular glands showed significant decreases during the first 7 to 14 days. The loss in weight was the greatest in the parotid gland. Histological and cytological observations indicated that the changes in secretory cells occurred in the following order: (1) beginning of nuclear pyknosis with a rapid decrease in number and size of nuclei by 24 hours after the injection; (2) advanced stages of nuclear pyknosis with concomitant decrease in cytoplasmic basophilia and granules by day 3; (3) apparent vacuolization and rarification of cytoplasm by day 7; (4) beginning of nucleolar and nuclear recovery by day 10; and (5) complete cytoplasmic recovery by the end of experiment as evidenced by the return of basophilia and disappearance of vacuoles. Paralleling the weight changes, cytological damages were greater in the parotid than in the submandibular acini. This was thought to be related to differences in nature of secretory products by the two organs. A decrease in number and pronounced irregularity in size of the granules in salivary ducts of the submandibular gland were observed but at a later time than the above mentioned changes in the acini. The significance of these changes has been discussed in light of the recently gained knowledge on the biosynthesis of nucleic acids and proteins as related to the chemical mechanism of actinomycin D in the inhibition of m-RNA synthesis.