BACKGROUND A recent systematic review and meta-analysis suggested that occupational exposure to endotoxins protects against lung cancer. To explore this hypothesis further, the follow-up of mortality of a cohort of 3551 workers, who were employed in the British cotton industry during 1966-1971, was extended by 23 years. METHODS Subjects had originally been recruited to a survey of respiratory disease, which collected information about occupation and smoking habits. Cumulative exposures to endotoxins were estimated from data on endotoxin levels by work areas in cotton mills. Risks of lung cancer were estimated using survival modelling. RESULTS During follow-up, 2018 deaths were recorded before the age of 90 years, including 128 deaths from lung cancer. After adjustment for smoking, hazard ratios (95% confidence intervals) for cumulative endotoxin exposures of ≤30,000, >30,000 and ≤200,000, >200,000 and ≤400,000, >400,000 and ≤600,000 and >600,000 endotoxin units (EU) m(-3) years were 1, 0.8 (0.5-1.6), 0.7 (0.4-1.3), 0.6 (0.3-1.0) and 0.5 (0.3-0.9), respectively (P for trend=0.005). CONCLUSIONS Our findings strengthen the evidence that occupational exposure to endotoxins protects against lung cancer, and suggest that the effect depends on cumulative dose and persists after exposure ceases.