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New agents are required in the treatment of malignant melanoma, to be used alone or in combination with established therapies. Oncostatin M (OSM), a member of the gp130 family of cytokines, has previously been shown to inhibit the growth of melanoma cell lines. Tamoxifen (TAM) is widely used in the treatment of melanoma, typically in combination with chemo- and/or immunotherapy. A component of the antitumour activity of TAM is via modulation of transforming growth factor-β (TGFβ) which has previously been shown to be synergistic with OSM in vitro. To further investigate the clinical potential of OSM, alone and in combination with TAM, set concentrations of each were added to nine fresh and two well-established melanoma cell lines. The proliferation of seven of the 11 cell lines was inhibited by OSM, while two were unresponsive at the dose range tested. Of particular interest was the finding that the growth of two of the cell lines was significantly stimulated at low doses of OSM. The combination of OSM with TAM produced widely divergent results, most frequently resembling the effects of OSM alone. No synergism between the two was evident in any of the cell lines tested. Our results indicate that a combination of OSM and TAM in clinical trials needs further evaluation before it can be recommended. Furthermore, while OSM alone may be useful in the treatment of melanoma, this may be complicated by the possibility of stimulating tumour growth in some instances.