Various cell stimuli act through activation of phospholipase A(2) resulting in the release of arachidonic acid, the precursor of eicosanoids, from the sn-2 position of cell membrane phospholipids. A byproduct of phospholipase A(2) activity is the lysophospholipids which have been found to potentiate T-lymphocyte activation. The purpose of the present study was to determine whether the various lysophospholipids modulate the migration of peripheral normal human T lymphocytes in vitro. It was found that lysophosphatidylchaline (lysoPC) induced T-lymphocyte migration in the concentration range 10(-7) to 10(-4) M with a maximum at 10(-6) M (mean chemotactic index, 2.06). The migration was due to chemotaxis rather than chemokinesis. In contrast, lysophosphatidylethanolamine (lysoPE) and lysophosphatidylinositol (lysoPI) did not exhibit chemotactic properties towards T lymphocytes. Further studies showed that the length of the fatty acids in the sn-1 position as well as the presence of double bonds modulated the chemotactic ability. The lysoPC compound with the highest chemotactic activity was lysoPC;1-palmitoyl (C = 16: 0). The results demonstrated that lysoPC, a phospholipase A(2)-generated hydrolysis product of phosphatidylcholine, induced T-lymphocyte chemotaxis in vitro. Because phosphatidylcholine is the major phospholipid in the epidermis, the activation of phospholipase A(2) may result in the release of lysoPC in concentrations capable of inducing migration of T lymphocytes into the epidermis.