The appearance of metastases is a characteristic feature of malignant tumor disease. Tumor hypoxia thereby tends to result in a significant increase of metastasis. The adaption of tumor cells to hypoxic conditions is basically driven by hypoxia-inducible transcription factors such as the hypoxia-inducible factor 1 (HIF-1). In vitro hypoxic HIF-1 activity can be modulated by nitric oxide. To investigate the effects of this modulation on hematogenous metastasis B16F10-melanoma cells were injected into the tail vein of C57Bl/6J-mice. Nodules visible on lung surface were counted fifteen days after injection. Twelve hours of hypoxic pre-incubation of B16F10-melanoma cells led to increased bulk of lung nodules. In contrast simultaneous pre-incubation with 100 mM DETA-NO completely eliminated this hypoxic effect. Parallel performed in vitro experiments showed a reduced hypoxic induction of the HIF-1 target gene carbonic anhydrase IX after the application of DETA-NO. Further in vitro and in vivo experiments with stable HIF-1 knock down B16F10-melanoma cells will provide evidence for the role of HIF-1 in hematogenous metastasis after NO exposure.