The biologically active sulfidopeptide leukotriene, leukotriene C4, is formed by the enzymatic action of leukotriene C4 synthase, which conjugates glutathione with leukotriene A4. We have found that a filarial glutathione S-transferase can function as a leukotriene C4 synthase. Glutathione S-transferase was purified from the cytosol of adult Dirofilaria immitis by glutathione-agarose affinity chromatography and was reacted with 25 microM leukotriene A4 methyl ester and 10 mM glutathione. The filarial enzyme catalyzed the formation of leukotriene C4 methyl ester, as shown by reverse phase high pressure liquid chromatographic analyses. The finding that filarial glutathione S-transferase can function as leukotriene C4 synthase provides a mechanism whereby filarial parasites could form lipoxygenase pathway derived sulfidopeptide leukotrienes.