The effect of ganglioside GM₃ on the endogenous protein phosphorylation of human monocytoid leukemia cell line J6-2 cells was studied.Addition of 100 μmol/L GM₃ to the particulate fraction of J6-2 cells enhanced the endogenous phosphorylation of several proteins whose relative molecular mass were 180,87,78,67,43 and 31kD while addition of 100 μmol/L GM₃ to the cytosol fraction of J6-2 cells stimulated the phosphorylation of several proteins whose relative molecular mass were 87 and 56kD,but could inhibit the phosphorylation of 70 and 43kD proteins. Because GM₃ has been reported to be able to induce J6-2 cells to differentiate along the monocyte/macrophage route by long term incubation with GM₃ (up to six days)，so the authors postulated that protein phosphorylation induced by short term GM₃ treatment might be the early signal of differentiation of J6-2 cells.