Male ESH guinea pigs were fed vitamin C deficient (0 mg/kg), adequate (200 mg/kg), or mega-supplemented (2000 mg/kg) diets for two weeks before acute (2hrs) exposure to cotton dust (35 mg/m³) or filtered air. This period of time was sufficient to produce mild scorbutic symptoms in the deficient animals and to significantly affect plasma levels of the vitamin. Breathing rates in 10% CO₂ were monitored for 18 hrs post-exposure, at which point the animals were anesthetized and the lungs lavaged to harvest alveolar macrophages and pulmonary leukocytes. Dietary vitamin C deficiency failed to enhance while vitamin C supplementation failed to protect against the cotton-induced increase in breathing rates, influx of leukocytes into the lung, and activation of alveolar macrophages. In fact, cotton exposed guinea pigs fed 0 mg/kg vitamin C had significantly lower breathing rates at 18 hrs post-exposure (200 breaths/min) than those fed 2000 mg/kg vitamin C (270 breaths/min). The cotton-induced increase in pulmonary leukocytes was slightly, but not significantly, greater in mega-supplemented guinea pigs. Moreover, the activity of alveolar macrophages, measured as the ability to produce superoxide anion in response to zymosan stimulation, was increased in cotton-exposed guinea pigs receiving mega-supplementation of dietary vitamin C. These findings contrast with studies in humans where vitamin C has been shown to protect against textile dust-induced bronchoconstriction. Rather than being protective, vitamin C appears to enhance the pulmonary responses of the guinea pig model to cotton dust exposure.