Compilation of 740 independent p53 mutations from a wide variety of human cancers was performed between 1989 and April 1992. Deletions or insertions were observed in 10% of the cases. Insertions ranged from 1 to 14 nucleotides. In 14 out of 16 cases, the inserted nucleotide(s) duplicated the sequence where it was inserted. The deletions ranged from one to 37 nucleotides. Twenty six cases were single nucleotide deletions and 19 of them were localized at iterated nucleotides. In all 26 deletions of two nucleotides or more, a direct repeat of 2-8 base pairs was present on the unaltered sequence in the close vicinity of the deletion. In 15 of these cases, the deletion removed a complete repeat and the entire region in between repeats. In the remaining cases, the deletion imperfectly removed one or both repeats and/or the intercalating sequence. Both p53 insertions and deletions can be explained by a slipped-mispairing mechanism as proposed for germinal mutations of a small number of eukaryotic genes. Less frequent than the deamination of 5-methyl cytosine in CpG dinucleotides, mutations resulting in loss or gain of nucleotide base pairs may represent the second highest endogenous mutagenic event for p53 gene in human cancers.