A specific, high-affinity binding site for leukotriene C4 was identified in human erythrocyte particulate fraction and in vesicle preparation. The binding was saturable, reversible and specific. Vesicle preparations showed that binding sites were localized on the outside of the plasma membrane. The dissociation constant and site density were found to be Kd = 15.9 +/- 3.2 nmol X 1(-1) and N = 152 +/- 35 sites per cell, respectively, as calculated from Scatchard analysis. The effect of leukotriene C4 did not modify the calcium influx and did not inhibit the ATPase-dependent calcium efflux. In this paper, the physiological significance of these sites is discussed.