Microsomal glutathione transferase (mGT) specifically binds leukotriene C4 synthase in the presence of Mg2+ ion (Söderström et al., Protein Expression and Purification (1995) 6, 352-356). To investigate if this interaction occurs in vivo we screened a human lung cDNA library with a bait vector encoding human mGT in the yeast two-hybrid system. One of the five positive clones obtained encoded leukotriene C4 synthase. This clone was expressed in two heterologous systems. The recombinant protein cross-reacted with a guinea pig antibody raised against a Keyhole limpet hemocyanin coupled synthetic peptide corresponding to amino acids 141-150 of human leukotriene C4 synthase.