Previous immunohistochemical studies on malignant mesothelioma with antibodies recognizing both the wild and the mutant types of the p53 protein have shown immunoreactivity in 25-70% of cases. This study was designed to determine whether there is immunoreactivity for p53 and mdm2 protein in malignant mesothelioma and to correlate p53 expression with the detection of mutations in p53 at DNA level. In 10 of 15 cases there was immunoreactivity for p53. In 6 of these cases immunoreactivity for mdm2 was also detected. In one p53-immunonegative case, a mutation of the p53 gene resulting in a stop codon was found. These results suggest that mdm2 might be involved in the inhibition of p53 in malignant mesothelioma. Also, these data suggest the existence of other proteins than mdm2 that may associate with p53.