Lysophosphatidic acid (LPA), a bioactive lipid produced by several cell types including postmitotic neurons and activated platelets, is thought to be involved in various biological processes, including brain development. Three cognate G protein-coupled receptors encoded by lpa₁ /lp _A1/Edg-2/Gpcr26, lpa₂ /lp _A2/Edg-4, and lpa₃ /lp _A3/Edg-7 mediate the cellular effects of LPA. We have previously shown that deletion of lpa₁ in mice results in craniofacial dysmorphism, semilethality due to defective suckling behavior, and generation of a small fraction of pups with frontal hematoma. To further investigate the role of these receptors and LPA signaling in the organism, we deleted lpa₂ in mice. Homozygous knockout (lpa₂ ^(−/−)) mice were born at the expected frequency and displayed no obvious phenotypic abnormalities. Intercrosses allowed generation of lpa₁ ^(−/−) lpa₂ ^(−/−) double knockout mice, which displayed no additional phenotypic abnormalities relative to lpa₁ ^(−/−) mice except for an increased incidence of perinatal frontal hematoma. Histological analyses of lpa₁ ^(−/−) lpa₂ ^(−/−) embryonic cerebral cortices did not reveal obvious differences in the proliferating cell population. However, many LPA-induced responses, including phospholipase C activation, Ca²⁺ mobilization, adenylyl cyclase activation, proliferation, JNK activation, Akt activation, and stress fiber formation, were absent or severely reduced in embryonic fibroblasts derived from lpa₁ ^(−/−) lpa₂ ^(−/−) mice. Except for adenylyl cyclase activation [which was nearly abolished in lpa₁ ^(−/−) fibroblasts], these responses were only partially affected in lpa₁ ^(−/−) and lpa₂ ^(−/−) fibroblasts. Thus, although LPA₂ is not essential for normal mouse development, it does act redundantly with LPA₁ to mediate most LPA responses in fibroblasts.