Unilateral ligation of the main excretory duct of the rat submandibular gland caused a progressive deterioration of secretory function characterized by: (1) the secretion of progressively smaller volumes of saliva in response to a standard maximal intraperitoneal (i.p.) dose of pilocarpine. Saliva volume was reduced 69.4, 88.8 and 95.9 per cent, respectively, 1, 3 and 7 days after duct ligation. By 2 weeks, the contralateral, non-ligated gland had an enhanced response to pilocarpine and the ligated gland a 96.8 per cent reduction in the volume of saliva secreted; (2) a progressive reduction in the maximum flow rates attained upon stimulation with pilocarpine, which were 23.4, 10.1 and 5.1 per cent of those attained in the contralateral gland at, respectively, 1, 3 and 7 days after ligation; (3) a progressive increase in the sodium concentrations of saliva, which became plasma-like 2 weeks after ligation; (4) a significantly reduced secretory response to standard doses of isoproterenol, phenylephrine, methoxamine and substance P 2 weeks after ligation. In addition, both cholinergic and adrenergic receptors were significantly reduced in number 2 weeks after ligation. Administration of daily injections of pilocarpine (10 mg, i.p.) after duct ligation reduced the gland atrophy observed 3 days (by 17 per cent) and 1 week (by 9 per cent) later, but did not prevent the reduction in volume or flow rats observed after duct ligation alone. Thus ligation of the main excretory duct causes a progressive dysfunction in acinar and duct cells in the rat submandibular gland and alters their responsiveness to physiological regulators of secretion. The alterations in glandular secretory function and in the composition of saliva which occur in diseases causing partial or complete obstruction to the flow of saliva are likely to be similar to the changes described.