Pigeon fanciers' lung (PFL) is a form of extrinsic allergic alveolitis caused by exposure to avian antigens. Although the mechanisms involved in the pathogenesis of PFL are unclear it has been suggested that immune complexes formed on the alveolar epithelial surface of the lung initiate the symptoms of the acute stages of discase. Pigeon intestinal mucin has been implicated as an important antigen in the pathogenesis of PFL, and affected fanciers have very high antibody titres against this antigen. In this study we investigated the IgG and IgG subclass responses to both intact and papain digested mucin in 250 pigeon fanciers classified according to the presence of absence of precipitating antibodies and clinical status. Sera were screened by quantitative ELISA for IgG and IgG subclass activity to these antigens. There was no significant difference in the median IgG titre to pigeon mucin in individuals with PFL and asymptomatic antibody positive individuals. IgG1 and IgG2 were the major antibody subclasses against pigeon intestinal mucin with lower titres of IgG3 and negligible IgG4. Patients with PFL had significantly higher titres of anti-mucin IgG1 than asymptomatic antibody positive individuals (p = 0.0019) whilst there was no significant differences in IgG2, IgG3 and IgG4 titres between these two groups. Papain digestion of mucin resulted in a 600 fold decrease in IgG3 titres whilst IgG1 and IgG2 titres were essentially unaffected as compared to undigested mucin. This suggests that both IgG1 and IgG2 are directed against the O-linked oligosaccharides in the papain resistant regions of mucin whilst the majority of IgG3 is directed against papain sensitive protein epitopes (or possibly N-Iinked sugars in the sparsely glycosylated regions). - The difference between symptomatic and asymptomatic sera in the IgG subclass profiles to pigeon intestinal mucin together with the very high titres of anti-mucin antibody in all individuals with PFL confirm pigeon mucin as a major antigen in disease. Differences in antibody subclass profiles are likely to affect the composition and properties of the immune complexes, with consequences for the developmcnt of disease.