The response of confluent monolayers of normal and cystic fibrosis (CF) pancreatic epithelial cells to stimulation by extracellular ATP and ATP analogues was investigated in terms of mucin secretion. Mucin secretion was measured as release of M1 antigens by a direct sandwich enzyme immunoassay. Extracellular ATP provoked rapid (≤15 min) and strong mucin secretion (+480 ± 35%) by the normal pancreatic cell lines but was not able to induce mucin secretion by the CF cell lines. The order of efficacy of nucleotide agonists with ATP > ADP > AMP > adenosine was that of typical P₂‐purinergic receptors. ATP induced a rapid and transient intracellular [Ca²⁺] mobilization in both normal and CF pancreatic epithelial cells. This work demonstrated that CFTR seemed to mediate ATP‐dependent mucin secretion.