Alternative splicing affecting the p53 carboxy-terminus has previously been described in mouse but not in normal human cells. We report here the detection in normal human lymphocytes of an alternatively spliced form of human p53 mRNA containing an additional 133 bp exon derived from intron 9. This splice variant encodes a truncated protein of 341 amino-acids including 10 new amino-acids derived from the novel exon. The truncated protein, which lacks part of the p53 tetramerization domain, fails to bind DNA in vitro and has a transcriptional defect in vivo in both yeast and mammalian cells. Quantitative RT-PCR experiments suggest that the alternatively spliced form is only present in significant amounts in quiescent cells. Considering the numerous functions ascribed to the carboxy-terminus of the p53 protein, this splice variant may have important implications for the biological role of p53 in normal cells.