Isolated rat lungs perfused with physiological buffer containing leukotriene C4 were found to rapidly metabolize leukotriene C4 to leukotriene C4 sulfoxide, leukotriene D4, and leukotriene E4. Addition of leukotriene C4 to the recirculating perfusion buffer was observed to cause a persistent increase in the pulmonary arterial pressure. Leukotriene C4 instilled into the airway of the perfused lung was also rapidly metabolized to these same products with retention of the products within the lung. In contrast, leukotriene B4 injected into the perfusion fluid was recovered unchanged in the lung effluent. Leukotriene B4 instilled into the airway of the perfused lung was observed to rapidly traverse the alveolar membranes and was recovered intact in the lung effluent. No evidence for formation of the 20-hydroxy or the 20-carboxy metabolites of leukotriene B4 by the isolated perfused rat lung was observed.