Clinical and immunological studies were made in forty-two patients diagnosed as suffering from hypersensitivity pneumonitis at Osaka Prefectural Habikino Hospital between 1973 and 1977. All the sera from forty-one patients tested had high titres of antibody against Cryptococcus neoformans in indirect fluorescent antibody tests, and twelve also had precepitins against Cryptococcus neoformans polysaccharide. Only about 10% of control sera from patients with other lung diseases had low titres of antibody against Cryptococcus neoformans. Antibody against Cryptococcus neoformans was also found frequently in the sera of asymptomatic members of the families of the patients. A possible relationship of Cryptococcus neoformans to hypersensitivity pneumonitis is suggested.