The aim of this review is to focus on the implication of the protein kinase C (PKC) family in gastric acid secretion. The acid production is complexly regulated integrating central and peripheral components. Besides the second messenger cAMP many studies aimed to elucidate the role of Ca2⁺ and diacylglycerol in acid response. Intracellular targets of Ca2⁺ and/or diacylglycerol are kinases like PKC or the calcium/calmodulin-dependent protein kinase II (CaMkinase II). The activation by both Ca2⁺ and diacylglycerol seemed to be restricted to PKC. Its activation is assumed of being mainly coupled to acetylcholine mediated by the muscarinic M₃ receptor. Acetylcholine increases the key effectors of protein kinase C diacylglycerol and calcium. Gastrin also increases the level of intracellular Ca2⁺ in isolated rabbit parietal cells but the implication for acid secretion remain unclear. Although a distinctive role of PKC in acid secretion signaling is widely accepted difficulties arise in specifying its precise function. PKC might not directly convey but might modulate the acid secretion signaling path.