There is evidence that the cellular responses to cytokines, such as granulocyte colony stimulating factor (G-CSF) and interferons, depend on prior activation of components of the JAK/STAT signalling pathway. We report here that the myeloid cell line NFS-60 shows aberrant JAK/STAT signalling yet elicits expected biological responses to G-CSF and interferons-alpha/beta and gamma. Instead of increased phosphorylation of JAK1 and JAK2 in response to G-CSF and interferon-gamma, and JAK1 and Tyk2 in response to interferon-alpha/beta, we observed only an increase of phosphorylation of Tyk2 in response to all of these cytokines in NFS-60 cells. The subset of STAT proteins being activated in response to these cytokines was unusual as well. G-CSF activated STAT3 and STAT5A, whereas interferons activated, in addition to STAT1 and STAT5 other, as yet unidentified, DNA binding proteins. However, NFS-60 cells show normal biological responses to these cytokines, such as proliferation in response to G-CSF, and reduction of proliferation, induction of an anti-viral response and induction of specific genes in response to interferons.