The effect of agents disrupting cholesterol-rich microdomains of the cell membrane was studied on the chemoattractant receptor (FPR and FRPL1) coupled effector responses of promyelocytic PLB-985 cells. Both methyl-β-cyclodextrin (MβCD) and filipin III inhibited exocytosis of primary granules and O2˙−-production induced by stimulation of either chemotactic receptor. Alteration of calcium homeostasis of MβCD-treated cells does not account for the impairment of the effector responses. Disruption of microfilaments by cytochalasin B (CB) partially reverses the inhibitory effect of cholesterol depletion. Our results provide functional support for the involvement of cholesterol-rich membrane domains in the signaling of chemotactic receptors and call the attention to the possible role of microfilaments in the organization of lipid microdomains. [Copyright &y& Elsevier]