The relationship between production of Colony-Stimulating Factor (CSF) and metastasis has been investigated in the TS/A murine model. CSF production was determined in TS/A cell variants isolated through serial in vivo selection of lung metastatic nodules induced by intravenous or subcutaneous injection of tumor cells (artificial and spontaneous metastases, respectively). All the cell variants selected for high artificial metastatic ability produced higher amounts of GM-CSF in vitro and stronger haematological alterations in vivo than cells obtained by serial selection of spontaneous metastases. Our data suggest that the late, rather than the early, steps of the metastatic process could be enhanced by GM-CSF production.