Normal human diploid fibroblasts (HDFs) stop dividing after a certain number of population doublings (PDs) in vitro. Telomere shortening observed at each cell division eventually leads telomeres to critical lengths, which in turn trigger growth arrest. Telomerase elongates the telomeres can immortalize HDFs without transformation. Stress-induced premature senescence (SIPS) establishes several at 72 h after exposure of HDFs to subcytotoxic concentrations of oxidative stressors such as hydrogen peroxide (H2O2). Oxidative stress can increase the shortening of telomeres in HDFs but much debate exists on whether SIPS results of telomere shortening or not. In order to understand the role of telomeres in the establishment of H2O2-induced SIPS, our stategy was to use a low-density cDNA array representing genes of general interest in cell biology to characterize gene expression of BJ HDFs and telomerase positive hTERT-BJ1 HDFs in H2O2-induced SIPS. In contrast to studying telomerase, we also wanted to investigate if we could induce SIPS by oxidative stress in HDFs derived from a patient with Werners syndrome (WS), and accelerated aging syndrome, which have increased DNA damage, and study gene expression patterns in WS HDFs. Finally, we also studied several transcription factors in BJ and hTERT-BJ1 HDFs in an attempt to explain the shift in gene expression observed as these cells enter SIPS.