Both the ERK1/2 and PI3-K pathways were important for the viability of myeloma cell lines. Flow cytometry was used to evaluate the effects of the indicated inhibitors and their combinations on the cell viability of ILKM2 and ILKM3 treated with 30 ng/mL IGF-I or insulin and of NOP2 treated with 1 ng/mL IL-6 for 2 days. The MEK1/2 inhibitor, U0126 (5 μM), and the PI3-K inhibitor, LY294002 (5 μM), similarly reduced the cell viability of myeloma cell lines (P < .01), and both together completely blocked the effects of IGF-I, insulin, or IL-6 (P < .001). The values of relative viable cell numbers are indicated by the means and SDs from 3 independent experiments. Statistical analysis by Student t test indicated significant differences of viable cell numbers between inhibitors that were or were not treated.