The ob gene product, leptin, is synthesized by adipocytes. In rodents, its main role is to regulate energy expenditure and food intake. The growth hormone (GH)-insulin-like growth factor (IGF) system is also ubiquitously expressed, is also involved in energy homeostasis and shares some of the signaling molecules of leptin and its receptors. Therefore, we have asked whether or not leptin interacts with the GH-IGF system in an in vitro model. SK-N-MC cells were chosen for further investigation since they express IGF-I, IGF-I receptor and IGFBP-2 mRNA and secrete IGF-I and IGFBP-2 protein. Specific leptin receptor mRNA, both short and long isoform transcripts, were identified in SK-N-MC cells by RT-PCR. Secondly and most importantly, when SK-N-MC cells were cultured in the presence of leptin, neither IGF-I, nor IGF-I receptor or IGFBP-2 mRNA expression was different than in the absence of leptin. In addition, an increase in leptin did not alter secretion of immunoreactive IGF-I or IGFBP-2 protein into cell culture medium. In conclusion, (1) human SK-N-MC neuroepithelioma cells express ob and leptin receptor mRNA and secrete leptin. (2) Added exogenous leptin does not affect IGF-I, IGFBP-2 or IGF-I receptor mRNA expression and IGF-I and IGFBP-2 secretion by SK-N-MC cells in vitro under the conditions studied. We hypothesize that leptin and the IGF system do not interact directly in a cell culture model of neuroepithelioma cells.