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Many cells exhibit plasticity. In neurons, plasticity is associated with learning and memory. Here we describe plasticity in epithelia similar to neurons. In neurons, a strong or repeated stimulus often results in enhanced release of neurotransmitters via a process known as sensitization. We discovered that intra‐airway acid challenge in pigs resulted in a sensitization‐like augmentation of mucus secretion in airway epithelia that persisted in vitro. Treating airway epithelia from normal pigs with neurotransmitter secretagogues in vitro also induced a long‐lasting augmentation of mucus secretion. Inhibition of protein synthesis or cAMP‐responsive element‐binding (CREB) protein, which are required for neuronal memory, prevented secretagogue‐mediated increases in mucus secretion in airway epithelia, whereas inhibition of CREB in vivo mitigated some features of acid‐induced sensitization. These observations …