We have previously used guinea pig tracheal rings to analyze the effect of cotton and other organic dusts on airway smooth muscle (ASM) contraction. In a recent epidemiologic study we documented that workers exposed to dust in the tobacco industry developed a high frequency of respiratory symptoms and ventilatory changes similar to those of textile workers. Water soluble extract of dust obtained from samples of tobacco leaves and associated dust were prepared as a 1:10 w/v solution by the method of Sheldon. Dose related contractions of nonsensitized GPT were demonstrated using the extracts. Pharmacologic studies were performed with indomethacin, pyrilamine, atropine, NDGA, acivicin, BPB, captopril and capsaicin. We also analyzed the contractile properties of different tobacco extract fractionated by molecular weight and lipid content. We suggest that tobacco extracts cause ASM contraction by non-immunological mechanisms involving mediators.