The search for genes responsible for the sensitivity of human cells to cell-killing effects of UV is an important area of biological research. To identify candidate genes responsible for UV sensitization, levels of mRNA expression were compared between W-sensitive RSa cells and UV-resistant variant UVr-1 cells, using a differential display method and Northern blot analysis. Messenger RNA expression levels of human Ras homologue enriched in brain (Rheb) and/or a Rheb-like gene were up-regulated and slightly decreased in UV-irradiated RSa and UVr-1 cells, compared to in mock-irradiated cells, respectively. RSa and UVr-1 cells, both of which were treated with antisense oligonucleotides for Rheb RNA, exhibited an increased resistance to UV cell-killing. It remains unclear why UVr-1 cells are resistant to UV yet express Rheb mRNA at high levels, However, the results of antisense experiments together with the up-regulation in W-irradiated RSa cells, suggest that Rheb is involved in the UV sensitization of both cells to UV cell-killing.