These effects were examined with and without pretreatment of animals with reserpine and the adrenergic antagonists prazosin (alpha 1), yohimbine (alpha 2) and propranolol (beta). The effects of clonidine on glandular concentrations of norepinephrine and dopamine also were examined. These effects were compared with those of xylazine, a presynaptic alpha 2-adrenergic agonist. A single, high dose of clonidine followed by an overnight fast caused marked increases in calcium content and acinar secretory granules in the submandibular and sublingual glands, similar to those caused by reserpine. However, the calcium content of the parotid gland was not altered by clonidine, although there seemed to be a modest increase in acinar secretory granules. The clonidine-induced increase in submandibular calcium content could not be attributed to any adrenergic receptor activity since it was not blocked by either alpha- or beta-adrenergic antagonists. Unlike reserpine, clonidine did not affect catecholamine concentrations in the parotid and submandibular glands. Pretreatment with reserpine did not significantly alter the clonidine-induced increase in submandibular calcium content. It is likely that the greater accumulation of acinar secretory granules is related to the increased calcium stores of the glands in clonidine- and/or reserpine-treated rats. The large differences in calcium content among the three glands might be attributable, in part, to differences in the calcium-binding capacity of their secretory granules. Possible mechanisms for the clonidine effects on salivary-gland calcium include disturbances in membrane-associated pools or gating mechanisms for calcium, which need further study.