Salivary epithelial functions are regulated by the autonomic nervous system. In this regard, we have been studying the morphology and neuroreceptor composition of A253, an immortal cell line isolated from a human submandibular carcinoma (Giard et al., JNCI, 51:1417-1421, 1973). Phase contrast and electron microscopic observations indicate that A253 cells are of epithelial origin. Physiologically, A253 cells possess beta-adrenergic, but not alpha-adrenergic or muscarinic-cholinergic receptors. The beta-adrenergic receptors (BARs) are composed primarily of a single class of high affinity, beta 2-subtype receptors as judged by [3H]dihydroalprenolol antagonist binding studies. The BARs are functional inasmuch as isoproterenol stimulation increases both intracellular cAMP content and [3H]mannose incorporation into endogeneous glycoproteins. Differences in ultrastructure and neuroreceptor composition between A253 and other immortal salivary tumor cell lines are discussed.