The ras gene is one of the oncogenes most commonly detected in human cancers; this protooncogene is converted to active oncogene by point mutations occurring at either codon 12, 13, or 61. SV40 is a DNA-transforming simian virus, a 105 bp sequence of which has been shown recently to be present in a significant fraction of human mesothelioma cells. Eleven human malignant mesotheliomas were examined for H-ras gene mutations at codon 12, 13, and 61 and for the presence of SV40-like sequences. DNA prepared from formalin-fixed and paraffin-embedded tissue was amplified by means of PCR and analyzed using designed restriction fragment length polymorphism. No mutation with respect to H-ras was found in any tumor sample, but the majority of mesothelioma cells contained SV40-like sequences.