p53 mutations are found in about 70% of human cancers. In order to evaluate the role of these mutations in response to chemotherapeutic agents, it is important to distinguish between p53 response to DNA‐damaging agents in normal and in tumour cells. Here, using normal human fibroblasts (NHFs), we show that cisplatin and UV radiation induce G₂/M arrest which is temporally linked to p53‐protein induction. To study the contribution of p53 to this G₂/M arrest, we inhibited p53 induction in NHFs using p53 anti‐sense oligonucleotides. Following exposure of NHFs to UV radiation, the inhibition of p53‐protein induction leads to a greater accumulation of cells in the G₂/M phase, but also to a decreased fraction of cells in the G₁ phase. We propose that p53 does not induce G₂/M arrest directly, and that the extent of this arrest may depend on the fraction of cells that do not stop at the G₁ phase following exposure to DNA‐damaging agents. Furthermore, inhibition of p53‐protein induction leads to increased sensitivity of NHFs to UV radiation. These results suggest that inhibition of p53 protein enhances sensitivity to DNA‐damaging agents in normal human cells. Int. J. Cancer 75:432–438, 1998. © 1998 Wiley‐Liss, Inc.