The muscarinic agonist bethanechol was infused intravenously, under α- and β-adrenoceptor blockade, in anaesthetized rats at various dose levels (5-10, 20 and 40-50 µg kg-1 min-1) over 30 min. The amount of saliva secreted from the parotid gland was dose dependent at 95, 202 and 737µl, respectively. The salivary amylase activity was approximately the same at the two lower doses (506 U and 448 U, respectively), while it was higher (1268 U) at the highest dose. In response to the highest dose, but not to the lower doses, the total parotid glandular amylase activity and the numerical density of parotid acinar secretory granules were lowered, by 25 % and 22 %, respectively. Thus, in the rat parotid gland, agonists such as bethanechol, which use Ca2+ as a second messenger, may release proteins not only by non-granular mechanisms but also, and in contrast to the general belief, by granule exocytosis. Experimental Physiology (2002) 87.2, 147-152.