Lysophosphatidic acid (LPA) from platelets and mononuclear phagocytes regulates T cell functions through endothelial differentiation gene‐encoded G protein‐coupled receptors (Edg Rs). Human blood unactivated CD4⁺ T cells express predominantly Edg‐4 LPA R over marginal levels of Edg‐2 LPA R, as assessed by semiquantitative PCR and Western blots. After mitogen activation, the CD4⁺ T cells express Edg‐2 Rs at approximately one half the level of Edg‐4 Rs. Secretion of IL‐2 by unactivated Edg‐4 R‐predominant CD4⁺ T cells incubated with anti‐CD3 plus anti‐CD28 antibodies was suppressed significantly and by up to 60% by 10⁻¹⁰ M to 10⁻⁶ M LPA, whereas secretion of IL‐2 by mitogen‐activated Edg‐2 R and Edg‐4 R codominant CD4⁺ T cells was enhanced by up to twofold by the same concentrations of LPA. The possibility that the two Edg Rs transduce different LPA signals to CD4⁺ T cells was supported by findings that IL‐2 secretion was inhibited by mouse anti‐Edg‐4 R monoclonal antibody, but enhanced by mouse anti‐Edg‐2 R monoclonal antibody. The separate effects of each LPA R were studied in Jurkat T cell transfectants expressing principally human Edg‐2 Rs (Jurkat‐T‐2) or Edg‐4 Rs (Jurkat‐T‐4) and stimulated with anti‐CD3 plus phorbol myristate acetate. LPA and anti‐Edg‐4 R antibody suppressed IL‐2 secretion by stimulated Jurkat‐T‐4 cells, whereas LPA and anti‐Edg‐2 R antibody enhanced IL‐2 secretion by stimulated Jurkat‐T‐2 cells. Activation‐induced alterations in the relative levels of Edg‐2 and ‐4 Rs on CD4⁺ T cells thus reverse the effects of LPA on T cell receptor‐stimulated generation of IL‐2.