Workers at a nylon plant developed pulmonary disease with systemic symptoms. Differentiating between humidifier fever and hypersensitivity pneumonitis (HP) is challenging. Cytophaga, an endotoxin-producing bacteria, was isolated from the plant air-conditioning system. A number of workers had systemic and pulmonary symptoms. Precipitins to Cytophaga endotoxin were identified. Several workers underwent lung biopsies demonstrating HP. Inhalation challenges with purified Cytophaga endotoxin were performed on three pairs of subjects: group 1, or employees with clinical features and biopsy consistent with HP; group 2, asymptomatic exposed workers with precipitins; and group 3, nonexposed healthy individuals. All subjects had fever and leukocytosis after inhalation challenge. Acute and/or late pulmonary function changes occurred in groups 1 and 2. Group 3 only had acute and transient pulmonary function changes. Cytophaga bacterial endotoxin is capable of inducing HP as well as humidifier fever.