Overexpression of the proto-oncogene c-fos induces transformation of primary avian and established rodent mesenchymal cells and tumor development in transgenic mice. As overexpression of Fos was also found in several human tumors of mesenchymal origin, we were interested whether c-fos is a transforming protein for human cells. Since fos genes transduced by infection competent vectors were most efficient in cellular transformation, expression cassettes of the human c-fos were introduced into a replication competent herpesvirus saimiri vector. Infection of human neonatal fibroblasts, cells of mesenchymal origin, resulted in episomal persistence of the recombinant viral genome and expression of c-fos in high excess. However careful examination for transformed phenotype failed to detect any changes in morphology, serum dependence, anchorage dependence, and life span, suggesting resistance of human mesenchymal cells against c-fos mediated transformation.