Several cases of interstitial lung disease have been diagnosed among workers at a nylon flock plant, but the etiologic agent for the disease outbreak was unknown. The results of a medical survey and industrial hygiene study indicated that the dust present in the plant may be responsible. Thus, airborne dust collected at the plant was examined for its inflammatory potential in rat lungs. The endpoints measured were: (1)breathing rates, (2) differential cell counts of bronchoalveolar lavage cells, (3) alveolar macrophage (AM) chemiluminescence, (4) albumin concentration and matrix metalloprotease activities in the acellular fluid from the initial bronchoalveolar lavage, and (5) pulmonary histopathology. In the first study, rats received a single dose of the airborne dust sample (10 mg/kg body weight) by intratracheal (IT) instillation. At 1 d post-IT, all inflammatory endpoints were significantly increased versus controls, but by 29 d post-IT they did not differ significantly from controls. Histopathology demonstrated mild to moderate, multifocal, suppurative pneumonia, usually centered around bronchioles, at 1 d post-IT. At 29 d post-IT, pulmonary inflammation was minimal to mild and characterized by alveolar histocytosis usually restricted to the immediate area of retained bire-fringent fibers. In subsequent experiments, airborne dust was extracted with water and the dust (washed airborne dust) and water extract (soluble fraction) were separated by centrifugation for further study. Nylon tow dust was prepared in the laboratory by milling uncut nylon strands (called tow) that had not been treated with the finish or dyes that are commonly used in the flock plants. Rats were administered a single dose of a dust sample (10 mg/kg body weight) or the soluble fraction (1.3 ml/kg body weight) by IT administration and the same endpoints were measured at 1 d post-IT. The dust samples caused significant increases in all of the inflammatory endpoints; however, the soluble fraction was much less active. Histological analysis of the lungs 1 d post-IT confirmed lung inflammation was occurring and tended to center around bronchioles. The results suggest that: (1) nylon flocking generates particles of respirable size that can interact with AM in the lung and can be detected in the lung 29 d after exposure, (2) the dust samples examined cause an inflammatory response, (3) water-extractable agent(s) from airborne dust contribute only minimally to the inflammatory response, and (4) the acute inflammatory response to these dusts is substantial when compared to other pathologic occupational dusts previously examined in our laboratory.