Leukotrienes (LTs) are 5-lipoxygenase metabolites derived from arachidonic acid and play important roles in many inflammation and allergic disorders. They are classified to two groups, LTB₄ and peptide-LTs. Both groups are thought to show their biological activities through their cellsurface receptors, but no LT receptor had been purified to homogeneity or cDNA-cloned. Recently, we cloned a cDNA for a LTB₄ receptor from HL 60 cells. The open reading frame of the cDNA encodes a protein of 352 amino acids and is predicted to contain seven membrane-spanning domains. In CHO cells stably expressing the LTB₄ receptor, LTB₄ elicited many signal transductions such as increase in intracellular calcium, InsP₃ accumulation, and inhibition of adenylyl cyclase. The CHO cells revealed a marked chemotactic response toward nM order of LTB₄. Next, we analyzed the signal transduction mechanisms through LTD₄ receptors using human monocytic leukemia THP-1 cells. When these cells were stimulated with LTD₄, intracellular calcium concentration was increased and MAP kinase was activated severalfold. This activation was mediated a protein kinase Cα-Raf-1 dependent pathway. A chemotactic response of THP-1 cells toward LTD₄ was observed. LT receptors transduce these signals through both PTX-sensitive and-insensitive G proteins.