Our previous work demonstrated that NIH-3T3 cells expressing high levels of the mutated cellular ras oncogene (Ej- ras gene) exhibited reduced hormone-sensitive adenylate cyclase and platelet-derived growth factor-stimulated (PDGF) phospholipase A 2 C activities. We now report that although the ras -transformed cells display markedly reduced phospholipase C activity, as measured by the levels of inositol 1,4,5-trisphosphate synthesized after PDGF-stimulation, normal levels of phospholipase A 2 activity can be uncovered; thus, similar levels of prostaglandin E 2 were synthesized in EJ- ras transformed and control cells after stimulation with phorbol myristate acetate (PMA) and/or the calcium ionophore A-23187, agents which stimulate protein kinase C and intracellular Ca 2+ levels, respectively. These data suggest that the EJ- ras gene product uncouples the PDGF receptor from the phospholipase C, resulting in reduced PDGF-stimulated Ca 2+ mobilization, protein kinase C stimulation and an apparent decrease in Ca 2+-dependent phospholipase A 2.