Upon exposure to collagen sponges, cultured adult human mesothelial cells were shown to differentiate into hematopoietic cells similar to those of the red bone marrow. This transformation was confirmed by morphological analysis and by cell immunoreactivity toward specific antibodies directed to antigens of the hematopoietic cell lines at various stages of differentiation. Besides demonstrating that the pluri-potentiality of the mesothelium persist into adulthood, this observation suggests that the process of differentiation may also be influenced by the structural organization of the microenvironment hosting the mesothelial cells.