In lesions of malignant melanoma, melanoma cells are exposed to various cytokines produced by inflammatory reactions. As a result, transformation of melanoma cells is expected to occur. We studied alterations in human melanoma cell line ganglioside composition after exposing melanoma cell lines to interferon (IFN)-gamma, interleukin (IL)-2, and IL-4 by biochemical methods. IFN-gamma increases the ratio of a-series gangliosides and the ratio of GM3/GD3. This suggests an alteration of immunoreactivity, a decrease in ganglioside sialyltransferase II activity, and an decrease in the malignant character of these cells. The alteration of the ganglioside profile varied among cytokines and cell lines. The progression of malignant melanoma may be influenced by reciprocal interactions between the melanoma cells and the host immune system.