Morphological and immunohistochemical features of the abdominal mesotheliomas that were developed by inoculation of 3 cell lines (MeET-4, -5 and -6) established from spontaneous abdominal mesotheliomas in male F344 rats. Although the original tumors of three cell lines showed signs of epithelioid growth with a predominantly simple papillary pattern, transplanted tumors revealed a variety of morphologic features including epithelioid with glandular structures, sarcomatous, and a mixture of these components. All tumor cells of transplanted tumors were positive for α-smooth muscle actin (ASMA) but almost negative for desmin as were epithelioid cells of the original tumors, and the cell lines were positive for desmin but not for ASMA. These results suggested that mesothelioma in the F344 rat had the potential for wide spectrum differentiation under in vitro conditions. The microenvironmental factors obtained in vivo can modify their potential ability and their morphological aspects. These factors may be related to tumor cell re-expression of ASMA of tumor cells that were masked under in vitro culture conditions.