Groups of guinea pigs were exposed to respirable particles of cotton dust obtained from opening and carding rooms of a textile mill. The bulk cotton dust was resuspended with a modified sonic sifter. Exposures were conducted 6 hr/day at concentrations varying between 16 and 25 mg/m3. The particle size for these exposures varied around a 3 micron aerodynamic equivalent diameter. In animals exposed for 5 days, a pulmonary effect began to develop 3 hr after the start of exposure on the first day and was maximal 18 hr postexposure. The pulmonary effect faded during the ensuing weekdays as daily exposures continued. In one group exposed for 6 weeks, 5 days/week, the pulmonary effect was apparent on each Monday and faded during the week. The pulmonary response can best be characterized as a reflex restriction of breathing from stimulation of vagal nerve endings, resulting in rapid shallow breathing. This effect was exaggerated upon challenge of the animals with air containing 10% CO2. In humans this pattern of rapid shallow breathing is associated with symptoms of shortness of breath, dyspnea, breathlessness, and fatigue upon exertion. Such symptoms are characteristic of those reported by workers exposed to cotton dust. This animal model is proposed for further evaluation of the possible relationship between the acute responses to cotton dust and the development of a chronic response.