We have previously used guinea pig tracheal (GPT) rings to analyze the effect of organic dusts on airway smooth muscle contraction. In a recent study we documented that workers exposed to dust in the poultry industry develop a high frequency of respiratory findings. A water soluble extract of dust obtained from poultry confinement buildings (PDE) was prepared as a 1:10 w/v solution by the method of Sheldon. Dose related contractions of nonsensitized GPT were demonstrated using the extract. PDE was added to the GPT's in 1/2 log increments in volumes of 10,30,100,300 and 1000 l. A series of 12 organ baths were used simultaneously. Each GPT was divided into 4 segments allowing us to examine three pharmacologic agents (and one control) in 3 animals at once. The effects of three mediator modifying drugs, indomethacin (10-5M), pyrilamine (10-5M) and LY171883 (10-5M) were studied as well as the effects of two enzyme inhibitors captopril (10-5M) and thiorphan (10-5M). Twelve animals were studied for each agent. Significant reductions in PDE induced contractions were demonstrated in GPT pretreated with all three mediator modifying agents. Similarly both enzyme inhibitors reduced PDE's effect on GPT. We conclude that 1) PDE causes dose related contractile responses in GPT, 2) Mediator modifying agents reduce PDE's contractile effect which is presumably the result of mediator release and 3) Enzyme inhibitors also reduce PDE's contractile effect by an as yet unexplained mechanism.