The GIMAP (GTPase of the immunity-associated protein) gene family includes seven functional members residing on human chromosome 7. GIMAP genes encode GTP-binding proteins that share a unique primary structure and whose function is largely unknown. However, gene ablation studies reveal that Gimap4 plays an important role in regulating the apoptosis of T cells. In a pilot microarray analysis on six cases of non-small cell lung cancer (NSCLC), we discovered that the expression of GIMAP family members, but not the neighboring non-GIMAP genes, was uniformly lower in the tumor tissues, compared to that in the adjacent nontumor tissues. This finding was subsequently confirmed by quantitative PCR assays in a total of twenty NSCLCs, and we found that GIMAP6 and GIMAP8 showed striking reduction of gene expression in the tumors. In contrast, GIMAP8 mRNA level was abnormally elevated in the adjacent nontumor tissues as compared to that in the control lung tissues. Such reciprocal expression of GIMAPs suggests that this unique gene family might contribute to the pathogenesis of and immune reactions to NSCLC.