We have examined the cytokine mRNA expression profile of six different human cell lines derived from Ewing sarcomas using polymerase chain reaction and found each to constitutively express a characteristic pattern. Furthermore, each cell line differed in the levels of secreted cytokines. We also analyzed the expression of several cytokines in murine UV-induced sarcomas and their heritably stable progressive variants. Each murine tumor also constitutively expressed a large number of cytokines, and in some cases, the more malignant variants differed from their parental tumors. These results demonstrate that tumors of the same type, and even in the same lineage, can have distinct cytokine expression and/or secretion profiles. Some cytokines may stimulate tumor growth while others may have antitumor effects. Cytokine therapy may be tailored depending upon the cytokine profile of the individual malignancy.