The human leukocyte receptor complex (LRC) on chromosome 19q13. 4 encodes Ig superfamily receptors expressed on hemopoietic cells. Killer Ig-like receptors (KIR) are expressed in cytotoxic lymphocytes but other LRC molecules (Ig-like transcript (ILT)/leukocyte Ig-like receptor (LIR)) are more ubiquitous. We investigated expression of the ILT2/LIR1 inhibitory receptor compared with the related KIR. Both ILT2/LIR1 and KIR were expressed by peripheral CD8+ T cells with a memory/effector phenotype. ILT2/LIR1+ T cells demonstrated diverse TCRBV repertoires in contrast to KIR+ T cells, while numbers of peripheral ILT2/LIR1+ T cells were greater than KIR+ T cells and the majority of ILT2/LIR1+ T cells did not coexpress KIR. Analysis of CD8+ T cells with specific HLA class I tetramers confirmed this pattern of expression, indicating differential regulation of LRC gene expression in T lymphocytes. Only a minor proportion of ILT2/LIR1+ KIR− clones survived in vitro cloning, were more susceptible to anti-CD3 or cognate peptide induced cell death than KIR+ T cells and exhibited lower levels of the Bcl-2 survival molecule. Our results indicate a sequential program of LRC-encoded receptor expression with initial ILT2/LIR1 expression in effector T cells and KIR gene transcription in the minor proportion of expanded clones which survives activation-induced cell death to become long term memory T cells.