GM-CSF is a hematopoietic cytokine that promotes the proliferation and differentiation of neutrophils, macrophages and other granulocytes. GM-CSF also has nonhematopoietic functions. GM-CSF receptors have been demonstrated on murine microglia, astrocytes, oligodendrocytes, neurons, and on human astrocytomas. This cytokine stimulates in vitro astrocyte proliferation, and has neurotrophic effects on cholineric neurons. It is not known whether these data are relevant to the developing human. Our objective was to determine the location of GM-CSF and its receptor in the human fetus. We obtained organs(including: brain, spinal cord, eye, heart, lung, liver, spleen, adrenal, kidney, intestine, placenta and clavicle) from fetuses of 8 and 16 weeks post conception. Using specific primers to identify GM-CSF and GM-CSF-R, RT- PCR was performed on extracted RNA from these tissues, as well as from human neuronal precursor cells (NT2), post mitotic differentiated neurons (hNT cells), and primary cultures of human astrocytes, and neurons. To determine the cellular specificity of these proteins, immunohistochemical localization was done using antibodies specific to human GM-CSF and its receptor. The presence of GM-CSF in spinal fluid from preterm and term neonates was also sought by specific ELISA. GM-CSF mRNA and protein was detectable in lung, spleen, adrenal, placenta and neural tissues. No GM-CSF was identified in spinal fluid. In contrast to GM-CSF, mRNA for the GM-CSF receptor was present in all organs tested, and in all cell culture samples. Cellular reactivity for GM-CSF-R in most organs was, however, limited to scattered macrophages, while in brain, both neurons and glials showed moderate staining. We conclude that although mRNA for GM-CSF-R was present in many organs, cellular reactivity was restricted to peripheral macrophages, and to cells within the CNS (neurons and astrocytes). We speculate that GM-CSF plays a role in neurodevelopment. Further studies are needed to determine its specific function in the developing human CNS.