We investigated the ability of a phospholipid cytokine, paf-acether to modulate programmed cell death in an immature human T cell line CEM-C12. Paf- acether alone did not cause cell death, but when it was added to CEM-C12 cells in the presence of calcium ionophore, a marked increase in cell mortality and DNA fragmentation was observed compared with calcium ionophore alone. This effect was dose-dependent between 2 and 10 μM paf-acether and specific in that lysophosphatidylcholine had a minimal effect. Thus, in association with another signal, paf modulates apoptotic processes in an immature human T cell line. This may be relevant to intrathymic lymphocyte maturation. © 1993 Academic Press, Inc.