Abstract23A2 myoblasts expressing GAP‐resistant, constitutively active G12V:H‐Ras (A2:G12V:H‐Ras myoblasts) display a transformed morphology and do not undergo mitogen‐deprivation‐induced differentiation or the associated apoptosis. To determine the phenotype induced by F156L:H‐Ras, a constitutively active mutant with enhanced nucleotide exchange activity rather than impaired GAP‐stimulated GTPase activity, myoblast cell lines were established that stably express F156L:H‐Ras at levels of H‐Ras comparable to the A2:G12V:H‐Ras myoblasts. These A2:F156L:H‐Ras myoblast cell lines do not possess a transformed morphology, and while differentiation and apoptosis are impaired, these processes are not abrogated as in the A2:G12V:H‐Ras myoblasts. Surprisingly, while expression of either G12V:H‐Ras or F156L:H‐Ras results in constitutive signaling through PI3‐kinase, only cells expressing G12V:H‐Ras additionally possess constitutive signaling through MAPK, and NFκB. Pharmacological abrogation of the Ras‐induced constitutive PI3‐kinase signal, however, is not responsible for the impaired differentiation or apoptosis in either A2:G12V:H‐Ras myoblasts or A2:F156L:H‐Ras myoblasts. Thus, our data suggest that a pathway distinct from those that signals through MAPK, NFκB or PI3‐kinase is responsible for the impaired differentiation and apoptosis in 23A2 skeletal myoblasts expressing constitutively active Ras.