The 5′ regions of the mouse, rat and human functional p53 genes were isolated and analysed. All three genes possess a non‐coding exon, comprising exclusively 5′ untranslated sequences. This exon contains extensive diad symmetry near the 5′ end of p53 mRNA, possibly allowing for the formation of a stable hairpin structure in this mRNA. The nucleotide sequence within this hairpin element is highly conserved among the species. A DNA stretch of 225 bp preceding the p53 mRNA cap site possesses distinct promoter activity when assayed in the CAT system. However, this activity is practically abolished when further upstream p53 sequences (approximately 120 bp) are included in front of the CAT gene. This suggests that the control of p53 gene expression is complex and involves a negative regulatory element.