The metabolism of leukotriene D4 to leukotriene E4 by a dipeptidase of kidney tissue is strongly inhibited by cilastatin (MK 0791) a known renal dehydropeptidase-I inhibitor. The comparison with similar enzyme activities from other tissues (liver, lung, serum, polymorphonuclear granulocytes) revealed a high specificity of cilastatin for the kidney enzyme which was found to be associated with the microsomal fraction. The lowest detectable inhibitory concentration of cilastatin within renal tissue was 8 X 10(-8)M.