Aberrations of the p53 gene and its transcript in ten human tumor-derived cell lines were investigated by single-strand conformation polymorphism analysis of polymerase chain reaction products. This method can detect loss of one of the two alleles and a point mutation in the remaining allele simultaneously. Aberrations were newly found in four tumor cell lines. Three cell lines had lost one of the alleles and had a point mutation in the other. These point mutations, resulting in amino acid substitutions, were in the region of the p53 gene, which is highly conserved in different species. All the mutated genes were expressed and produced mRNAs with point mutations. One cell line did not contain any detectable transcript of the p53 gene, although no structural aberration of the gene was detected in the regions analyzed. Most of the cell lines found to carry aberrations of the p53 gene in this work have previously been reported to have mutations in oncogenes or in a tumor suppressor gene other than the p53 gene. These results provide additional examples of multiple genetic changes in the genesis of human tumors.