The ligation of G protein–coupled chemokine receptors induces multiple pathways linked to different G-protein subunits. The classic analysis of chemokine receptor activation is the measurement of Ca2+ flux, but several other pathways exist that may influence cellular activation and mediator production. The α subunit appears to be coupled to at least 4 different pathways that can influence arachidonic acid metabolism, as well as to MAP kinase activation pathways. The other 2 subunits, β and γ, combine to mediate the chemotactic process and initiate the Ser/Thr and Tyr kinase and phosphatase pathways. Altogether, G-protein activation pathways may help to regulate or activate the leukocytes after they become ligated. It is unclear how the activation of specific pathways is managed under different chemokine stimuli.