Background: A study was performed to assess the acute association between air pollution, pollen and spores, and mortality in a population based cohort of subjects with asthma recruited from emergency room admissions for an asthma exacerbation using a case crossover design. Methods: Patients in Barcelona aged over 14 years who died during the period 1985-95 who had visited the emergency department of one of the four largest hospitals in the city for asthma during 1985-9 were included in the study (a total of 467 men and 611 women). Deaths were identified by record linkage of the cohort individuals with the Catalonia mortality registry. Causes of death were based on the underlying cause on the death certificate. Air pollution, pollen and spore levels were measured at the city monitoring stations which provide an average for the entire city. Results: Nitrogen dioxide was associated with mortality for all causes of death (adjusted odds ratio (OR) for an increase of the interquartile range = 1.50, 95% confidence interval (CI) 1.09 to 2.64) in asthmatic patients with more than one emergency room admission for asthma. The association was particularly strong for respiratory causes (OR 1.63, 95% CI 0.93 to 2.86). Ozone also increased the risk of death in asthmatic patients (OR 1.90, 95% CI 1.09 to 3.30) during spring and summer. The association with particles, pollen, and spores was not significant, and no interactions between air pollutants and pollen and spores were found. Conclusion: Nitrogen dioxide and ozone may exacerbate severe asthma and even cause death among asthmatic subjects.