Autotransplantation of the submandibular gland is effective for severe keratoconjunctivitis sicca. However, most transplants show decreased secretion shortly after the operation, which leads to obstruction of Wharton's duct. The hypothesis that decreased catecholamine release due to denervation contributes to hypofunction in the early phase was tested in transplanted glands in rabbits. We found that salivary flow, expression of beta(1)- and beta(2)-adrenoceptor, and the maximum binding capacity were markedly decreased in the transplanted glands. Isoproterenol significantly reversed the decreased secretion, enhanced the expressions of beta(1)- and beta(2)-adrenoceptor, and ameliorated the atrophy of acinar cells. The contents of cAMP and phospho-ERK 1/2 were increased after isoproterenol treatment. These results indicate that lack of beta-adrenoceptor stimulation is involved in early dysfunction of the transplanted gland. Isoproterenol treatment moderates structural injury and improves secretory function in the transplanted submandibular gland through up-regulating beta(1)- and beta(2)-adrenoceptor expression and post-receptor signal transduction.