Background: Lysophosphatidic acid (LPA) is a membrane-derived lysophospholipid with wide ranging effects on multiple lung cells including airway epithelial and smooth muscle cells. LPA can augment migration and cytokine synthesis in lymphocytes, but its potential effects on Th2 cytokines has not been well studied. Objective: We examined the effects of physiologic concentrations of LPA on IL-13 gene expression in human T cells. Methods: The Jurkat T cell line and human peripheral blood CD4+ T cells were incubated with LPA alone or with: (i) pharmacologic agonists of different signaling pathways, or (ii) antibodies directed against the T cell receptor complex (anti-CD3) and co-stimulatory molecules (anti-CD28. Cytokine secretion was measured by ELISA, and by bioassay investigating Stat6 phosphorylation in primary bronchial epithelial cells. Luciferase-based reporter constructs driven by different lengths of the human IL-13 promoter were transfected by electroporation in Jurkat cells treated with and without LPA. The effects of LPA on IL-13 mRNA stability were examined using actinomycin D to halt ongoing transcription. Expression of LPA receptors was analyzed by RT-PCR and/or Western blot assay. Results: Both Jurkat and CD4+ T cells constitutively express the LPA receptors LPA₁ and LPA₂. Expression of mRNA encoding LPA₂ and lipid phosphate phosphatase-1 (LPP-1) increased with T cell activation. LPA augmented IL-13 secretion under conditions of submaximal T cell activation. This was observed using pharmacologic agonists activating intracellular calcium-, protein kinase C-, and cAMP-dependent signaling pathways, as well as antibodies directed against CD3 and CD28. LPA only slightly prolonged IL-13 mRNA half-life in submaximally stimulated Jurkat cells (7.9 to 8.3 hrs). In contrast, LPA significantly enhanced transcriptional activation of the IL-13 promoter via regulatory elements contained within the proximal 312 base pairs. The effects of LPA on IL-13 promoter activation appeared to be distinct from those mediated by GATA3. Conclusion: LPA can augment IL-13 gene expression in T cells, especially under conditions of submaximal activation.