In blast cells obtained from patients with acute myelogenous leukemia, p53 mRNA was present in all the samples examined while the expression of p53 protein was variable from patient to patient. Mutations in the p53 gene are infrequent in this disease and, hence, variable protein expression in the majority of the samples cannot be accounted for by mutation. In this study, we examined the regulation of p53 gene expression in human leukemic blasts and characterized the p53 transcripts in these cells. We found control both at the level of RNA abundance and at the level of translation. Four experiments point towards translational control of human p53 gene expression. First, there is no correlation between the level of p53 mRNA and the level of p53 protein expression in blast cells. Second, in two cell lines with similar levels of p53 protein expression but with different levels of p53 mRNA, we find that there is preferential association of p53 mRNA with large polysomes in the cells with less p53 RNA. Third, translation of synthetic human p53 transcripts in cell-free extracts is inhibited by the p53 3'UTR. Fourth, the p53 3'UTR, when present in cis, can repress translation of a heterologous transcript. These observations raise the possibility that human p53 mRNA translation may be regulated in vivo by RNA binding factors acting on the p53 3'UTR.