Fragmented lung tissue prepared from human, ferret and guinea pig converted [3H]-leukotriene C4 ([3H]-LTC4) to [3H]-LTD4 and [3H]-LTE4. [3H]-LTD4 was the major product recovered from incubations with human and guinea pig lung, whereas [3H]-LTE4 was the predominant metabolite in ferret. Kinetic analysis in human lung yielded a much faster rate for the conversion of [3H]-LTC4 to [3H]-LTD4+E4 than for the conversion of [3H]-LTD4 to [3H]-LTE4. In all three species serine-borate complex blocked the metabolism of [3H]-LTC4, whereas L-cysteine blocked the metabolism of [3H]-LTD4. These studies demonstrate that guinea-pig and human lungs have a similar metabolic pattern and capacity which is dissimilar to the ferret.