Respiratory disease is important in horses, particularly in young Thoroughbred racehorses, and inflammation that is detected in the trachea and bronchi (termed inflammatory airway disease [IAD]) is more significant in this population in terms of impact and frequency than other presentations of respiratory disease. IAD, which is characterized by neutrophilic inflammation, mild clinical signs, and accumulation of mucus in the trachea, may be multifactorial, possibly involving infections and environmental and immunological factors, and its etiology remains unclear. This 3-year longitudinal study of young Thoroughbred racehorses was undertaken to characterize the associations of IAD and nasal discharge with viral and bacterial infections. IAD was statistically associated with tracheal infection with Streptococcus pneumoniae (capsule type 3), Streptococcus zooepidemicus, Actinobacillus spp., and Mycoplasma equirhinis and equine herpesvirus 1 and 4 infections, after adjustment for variation between training yards, seasons, and age groups. The association with S. pneumoniae and S. zooepidemicus was independent of prior viral infection and, critically, was dependent on the numbers of organisms isolated. S. pneumoniae was significant only in horses that were 2 years old or younger. The prevalence and incidence of IAD, S. zooepidemicus, and S. pneumoniae decreased in parallel with age, consistent with increased disease resistance, perhaps by the acquisition of immunity. The study provided evidence for S. zooepidemicus and S. pneumoniae playing an important etiological role in the pathogenesis of IAD in young horses.Respiratory disease is common in racehorses in training (10,15,29), as it is in most young domestic animals species. Both the incidence and prevalence of respiratory disease in racehorses vary widely between yards and between years (38, 46, 58), but the reasons underlying this variation, including the causes of the disease, are not defined.Inflammatory lower airway disease (IAD), which is usually associated with increased amounts of mucus visible in the trachea after exercise and increased proportions of inflammatory cells (44), is common in young racehorses around the world, despite marked differences in management and climate. Clinical signs associated with IAD include coughing (10, 16) and poor performance in racing (30,37,44,45). IAD is considerably more common than signs of upper respiratory disease and in young racehorses has a mean monthly prevalence of around 12% and an incidence of around 10 cases/100 horses/month (10, 58). The mean duration of each incident is around 8 weeks, and the disease is often recurrent in individuals. The monthly prevalence and incidence of signs of upper respiratory disease are around 5% and 5 cases/100 horses/month (10, 38, 58).The etiology and pathogenesis of IAD are poorly defined, but the etiology is probably multifactorial (10, 44). Studies focusing on individual agents suggest the possible involvement of viral infection (59), bacterial infection (10,14,16,42,43,56), and...