The association of chronic mucus hypersecretion and mortality is a matter of debate. We wished to determine whether the relationship between chronic mucus hypersecretion and chronic obstructive pulmonary disease (COPD)-related mortality could be explained by proneness to pulmonary infection. We followed 14,223 subjects of both sexes for 10-12 yrs. Cases where COPD was an underlying or contributory cause of death (n = 214) were included, and hospital records were obtained when possible (n = 101). From the presence of increased mucus, purulent mucus, fever, leucocytosis and infiltration on chest radiography, death was classified as either due to pulmonary infection (n = 38), other causes (n = 51), or unclassifiable (n = 12). Of subjects reporting chronic mucus hypersecretion at the initial examination, pulmonary infection was implicated in 54% of deaths, whereas this only occurred in 28% of subjects without chronic mucus hypersecretion. Controlling for covariates, in particular smoking habits, a Cox analysis showed a strong inverse relationship between ventilatory function and COPD-related mortality. Chronic mucus hypersecretion was found to be a significant predictor of COPD-related death with pulmonary infection implicated (relative risk (RR) 3.5) but not of death without pulmonary infection (RR 0.9). We consider that subjects with COPD and chronic mucus hypersecretion are more likely to die from pulmonary infections than subjects without chronic mucus hypersecretion. This may explain the excess mortality in subjects with COPD and chronic mucus hypersecretion found in previous studies.