Sphingosine 1‐phosphate (S1P) from platelets and macrophages stimulates migration and enhances survival of T cells. Mouse spleen CD4 and CD8 T cells are shown to express predominantly S1P₁ (Edg‐1) and S1P₄ (Edg‐6) G‐protein‐coupled receptors with only minimal representation of S1P₂, S1P₃, and S1P₅. At and below plasma concentrations of healthy mammals (1 nM–1 μM), S1P evokes trans‐Matrigel chemotaxis of mouse CD4 and CD8 T cells and recruits T cells into subcutaneous air pouches. T cell receptor‐mediated activation of CD4 T cells suppresses expression of S1P₁ and S1P₄ receptors and eliminates their chemotactic responses to S1P. The immunoregulator FTY720, a structural homologue of S1P, lacks T cell chemotactic activity and competitively inhibits T cell chemotactic responses to S1P in vitro and in vivo. S1P may be a distinctive contributor to compartmental immunity by attracting naïve and memory T cells preferentially over activated effector T cells.—Graeler, M., Goetzl, E. J. Activation‐regulated expression and chemotactic function of sphingosine 1‐phosphate receptors in mouse splenic T cells. FASEB J. 16, 1874–1878 (2002)