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 lysophosphatidylcholine (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 ehemotactic ability. The lysoPC compound with the highest chemotactic activity was lysoPC;1-palmitoyl (C = 16: 0). The results demonstrated that lysoPC, a phospholipase A2-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.