Uridine 5'-triphosphate (UTP, INS316) is a naturally occurring agonist for P2Y(2) receptors on the apical surface of ciliated respiratory epithelium. INS316, being developed by Inspire Pharmaceuticals, is a short-acting, aerosolized uridine 5-triphosphate (UTP) solution used as a diagnostic aid for lung cancer. INS316 appears to improve sputum expectoration mediated through the P2Y2 receptor, a nucleotide receptor expressed in human airway epithelial cells and some other tissues. UTP binding to the P2Y2 receptor triggers signal transduction that leads to chloride ion secretion, thereby resulting in mucociliary clearance of airway. UTP stimulates salt and water transport and cilia beat frequency in human airway epithelium in vitro. Single, inhaled doses of UTP stimulate mucociliary clearance in conscious, intubated sheep and in patients with mild chronic bronchitis (smokers and former smokers), suggesting that UTP may be useful for obtaining deep-lung sputum specimens suitable for diagnostic purposes. A single dose of INS316 safely improves the ability of patients with mild chronic bronchitis to expectorate a deep-lung sputum specimen suitable for cytologic evaluation.