We have synthesized the 5,6-LTA4, 8,9-LTA4, and 14,15-LTA4 as methyl esters by an improved biomimetic method with yields as high as 70-80%. We have investigated the catalytic efficiency of the purified cytosolic glutathione S-transferase (GST) isozymes from rat liver in the conversion of these leukotriene epoxides to their corresponding LTC4 methyl esters. Among various rat liver GST isozymes, the anionic isozyme, a homodimer of Yb subunit, exhibited the highest specific activity. In general, the isozymes containing the Yb subunit showed better activity than the isozymes containing the Ya and/or Yc subunits. Interestingly, all three different LTA4 methyl esters gave comparable specific activities with a given GST isozyme indicating that regiospecificity of GSTs was not the factor in determining their ability to catalyze this reaction. Surprisingly, purified GSTs from sheep lung and seminal vesicles showed little activity toward these leukotriene epoxides, indicating a lack of the counterpart of rat liver anionic GST isozyme in these tissues.