We have investigated the p53 gene, expression of its mRNA, and stabilization of its protein in a series of non-Hodgkin's lymphomas (NHLs). Immunohistochemistry revealed positive staining of the p53 protein in node biopsies from 6/36 NHL patients, all of whom had high-grade disease. The remaining NHL samples, together with 3 reactive nodes, showed either negative staining or the staining of only occasional cells. In one case that exhibited intense nuclear staining in 90% of the cells, a mutation in the p53 gene was also observed. There was no evidence of rearrangements of the p53 gene in any of the NHL samples. Although p53 mRNA could not be detected in nonmalignant tissue, it was apparently overexpressed in 16/38 NHL, but this did not correlate with positive staining of the p53 protein. These data suggest that p53 dysfunction might play an important role in the evolution of some cases of NHL, and that mechanisms other than mutation of the p53 gene may be involved in stabilizing the p53 protein in these neoplasms.