Tetrandrine is an alkaloid isolated from the root of a traditional Chinese medicinal herb. Tetrandrine has been shown to inhibit the secretion of fibrogenic or inflammatory substances from alveolar macrophages. The objective of the present study was to determine if tetrandrine is effective in preventing pulmonary inflammation and increased breathing rate characteristic of the response of guinea pigs to cotton dust exposure. In unexposed animals, oral administration of tetrandrine (33 µg/g body wt) for 5 days had little effect on the number of lavagable macrophages or leukocytes. However, in these unexposed guinea pigs, tetrandrine did inhibit breathing rate and the ability of macrophages to secrete superoxide anion in response to zymosan particles. In contrast, with cotton dust exposure, tetrandrine pretreatment accentuated cotton dust-induced increases in breathing rate, number of lavagable leukocytes, and secretory activity of alveolar macrophages. Therefore, tetrandrine did not prove useful in preventing the pulmonary response of guinea pigs to inhalation of cotton dust.