High levels of circulating interleukin-6 (IL6), and possibly neuroendocrine (NE) differentiation, correlate with advanced prostate cancer (PCa). IL6 has many overlapping biological effects with the related gp130 cytokines LIF and OSM that can be explained by the shared usage of the signalling receptor, gp130. We set out to determine whether LIF and OSM can substitute for IL6 in PCa, particularly in relation to neuroendocrine differentiation. Expression analysis of the gp130 cytokines and receptors by RT-PCR, Southern blotting and immunohistochemistry showed that they are widely expressed in LNCaP, DU145 and PC3 cells, but not in normal prostate epithelial PZ-HPV-7 cells. IL6, but not LIF or OSM inhibited proliferation, induced NE differentiation and tyrosine phosphorylation of STAT3 in LNCaP cells. The data suggests that IL6 has a unique role in the progression of PCa.