Rat-pancreas lobules were incubated with the ionophore A-23187 in the presence of Ca2+. After 90 min, some of the acini were partially or almost completely depleted of their zymogen granules while others had the appearance of resting acini. With few exceptions, the cells of a given acinus were degranulated to a comparable level. Slight dispersion of the zymogen granules was noticed in cells incubated in a Ca2+-free medium containing EGTA with or without A-23187. In the presence of Ca2+ the secretory response obtained with the ionophore was comparable to that observed with 10(-5)M urecholine. The results obtained provide cytological evidence that the secretory response is only partially determined at the membrane-receptor level and that other mechanisms intervene between cytosol Ca2+ increase and exocytosis.