Yoshio Maruyama and I summarized our discovery and characterization of Ca2+-activated ion channels in epithelial cells in a review article published 25 years ago (Petersen and Maruyama, 1984). Ca2+- and voltage-activated high-conductance K+ channels as well as Ca2+-activated non-selective monovalent cation channels were located in the baso-lateral membranes of exocrine acinar cells, whereas Ca2+-activated Cl- channels were proposed to be located in the apical (luminal) membrane. We only proved the specific Cl- channel localization many years later (Park et al. 2001). In recent years, high-resolution confocal and two-photon studies of the dynamics of [Ca2+] in the cytosol, all major organelles and the immediate extracellular environment of pancreatic acinar cells have provided a detailed understanding of physiological (Petersen & Tepikin, 2008) and pathological (Petersen et al, 2009) Ca2+ signalling processes. Studies on pancreatic acinar cells have shown that intracellular trypsin activation, which initiates the often fatal human disease acute pancreatitis, is initiated by global sustained elevations of the cytosolic Ca2+ concentration (Petersen et al, 2009). Recent data from my laboratory, involving studies on pancreatic acinar cells isolated from IP3 receptor knock -out mice, have shown directly that trypsin activation elicited by non-oxidative alcohol metabolites depends specifically on excessive Ca2+ release via acid store IP3 receptors of types 2 and 3 (Gerasimenko et al. 2009). This study has for the first time identified the mechanism of alcohol-related acute pancreatitis.