In the lungs of cystic fibrosis patients, overproduction of mucus leads to morbidity and mortality by obstructing airflow and shielding bacteria from antibiotics. Here we demonstrate that overproduction of mucus is a direct result of the activation of mucin gene expression by Gram-positive bacteria. Bacterial lipoteichoic acid activates the platelet-activating factor receptor, which is G protein–coupled. This results in activation of a disintegrin and metalloproteinase (ADAM10), kuzbanian, cleavage of pro heparin–binding epidermal growth factor and activation of the epidermal growth factor receptor. Unlike responses in macrophages, the epithelial-cell response to lipoteichoic acid does not require Toll-like receptor 2 or 4.