Ganglioside composition of human melanoma was correlated with sensitivity of melanoma to antitumor treatment with chemotherapeutic agents and radiation. The cytotoxic effect of each treatment was evaluated on 16 melanoma cell lines using the human tumor colony-forming assay. Ganglioside fractions were extracted and purified from each cell line and analyzed for the four major gangliosides in melanoma (GM3, GM2, GD3, and GD2) by thin-layer chromatography (TLC) and TLC scanner. GD2 content positively correlated with sensitivity to radiation (r = 0.753, p less than 0.001) and vincristine (r = 0.779, p less than 0.001). In contrast, GM3 content inversely correlated with sensitivity to radiation (r = -0.658, p less than 0.01) and vincristine (r = -0.692, less than 0.01). The gangliosides GD3 and GM2 were shown to have no significant correlation with any of these treatments.