The effects of p-octopamine injected i.v. and i.p on salivary flow rates and proteins secreted by the submandibular glands of rats were studied with and without various types of autonomic blockers at different doses, and with two enzyme inhibitors. The salivary flow rates and the amounts of protein secreted progressively increased with increasing doses injected both i.v. and i.p., whereas they were dramatically reduced with almost all autonomic blockers and disulfiram, a dopamine-beta-hydroxylase inhibitor. Salivation was completely abolished in response to p-octopamine in combination with metoprolol or phenoxybenzamine at high doses, and simultaneous injections of prazosin and propranolol. The concentration of protein in submandibular saliva in response to p-octopamine injected i.v. and i.p. was not dose-dependent and significantly increased with all of the alpha-blockers except yohimbine, and with atropine and disulfiram. The protease activity was dose-dependent but was reduced significantly with alpha-blockers except yohimbine and with two enzyme inhibitors. The alpha-type of protein was secreted in response to p-octopamine injected i.v. and i.p. at all doses except with the lowest dose i.p., which caused the beta-type to be secreted. The alpha-type was completely replaced by the beta-type with all alpha-blockers at all doses, except with yohimbine, but no change was observed with various types of beta-blockers, yohimbine, atropine, and two enzyme inhibitors. Thus, p-octopamine could stimulate both the alpha- and beta-adrenoceptors in the submandibular glands of rats.