Expression levels of mRNA in peripheral blood mononuclear cells from five renal transplant recipients and five non-transplanted controls were analyzed with GeneChips (GeneChip Instrument system, Affymetrix, Santa Clara, CA, USA). All recipients had retained a well-functioning kidney graft for more than 15 yr on low-dose maintenance immunosuppression. Among a total of 12630 transcripts examined, significant differential expression was observed for 599 genes, whereby 470 genes were up-regulated and 129 down-regulated in the transplant recipients compared with controls. Of these, 192 up-regulated and 46 down-regulated genes showing a change greater than twofold were divided into eight functional categories as follows (numbers of genes, up/down): immune system (12/14), cell proliferation (17/3), oncology (15/3), transporter/receptor/binding protein (16/5), transcription factors (8/2), enzymes (17/4), expressed sequence tags (91/9), and others (16/6). Predictably, expression of immune-associated genes was decreased in the recipients. Significant reduction of expression levels of CD3, ICAM-1, and B7.2, which are critical molecules for interactions between antigen presenting cells and T cells, were observed. In T cell signal transduction, the Ras pathway was likely to be suppressed by activation of hVH-5. The present data help to elucidate the immunological status in long-term kidney graft recipients and may provide insights for future regimens to establish donor-specific hyporesponsiveness.