The presence of peritoneum-based, cytokeratin-positive tumor cells, as detected under conditions of intravenous inoculation of chickens with a v-src-positive DNA fragment, raised the possibility that such DNA may be inductive for diffuse mesothelioma. To investigate this possibility, chickens were inoculated intraperitoneally with v-src DNA, and the resultant peritoneum-based tumor tissue was subjected to histopathological analysis. On the basis of (i) morphology, (ii) immunohistochemistry/histochemistry, and (iii) ultrastructure, we concluded that this tissue represents a diffuse mesothelioma.