Pancreatic acini secrete digestive enzymes in response to a variety of secretagogues including cholecystokinin and agonists acting via proteinase-activated receptor-2 (PAR2). We employed the cholecystokinin analogue caerulein and the PAR2 activating peptide SLIGRL-NH₂ to compare and contrast Ca²⁺-changes and amylase secretion triggered by CCK and PAR2 stimulation. We find that secretion stimulated by both agonists is dependent upon a rise in cytoplasmic Ca²⁺ ([Ca²⁺]_i) and that this rise in [Ca²⁺]_i reflects both the release of Ca²⁺ from intracellular stores and accelerated Ca²⁺influx. Both agonists, at low concentrations, elicit oscillatory [Ca²⁺]_i changes and both trigger a peak-plateau [Ca²⁺]_i change at high concentrations. Although the two agonists elicit similar rates of amylase secretion, the rise in [Ca²⁺]_i elicited by caerulein is greater than that elicited by SLIGRL-NH₂. In Ca²⁺-free medium, the rise in [Ca²⁺]_i elicited by SLIGRL-NH₂ is prevented by prior addition of a supramaximally stimulating concentration of caerulein but the reverse is not true - the rise elicited by caerulein is neither prevented nor reduced by prior addition of SLIGRL-NH₂. Both the oscillatory and the peak-plateau [Ca²⁺]_i changes that follow PAR2 stimulation are prevented by the phospholipase C (PLC) inhibitor U73122 but U73122 prevents only the oscillatory [Ca²⁺]_i changes triggered by caerulein. We conclude that (a) both PAR2 and CCK stimulation trigger amylase secretion that is dependent upon a rise in [Ca²⁺]_i and that [Ca²⁺]_i rise reflects release of calcium from intracellular stores as well as accelerated influx of extracellular calcium; (b) PLC mediates both the oscillatory and the peak-plateau rise in [Ca²⁺]_i elicited by PAR2 but only the oscillatory rise in [Ca²⁺]_i elicited by CCK stimulation; (c) the rate of amylase secretion elicited by agonists acting via different types of receptors may not correlate with the magnitude of the [Ca²⁺]_i rise triggered by those different types of secretagogue.