The purpose of the present study was to determine the distribution of granulocyte-macrophage colony-stimulating factor (GM-CSF) and its receptor (GM-CSF-R) in the human fetus. We used reverse transcription PCR to detect GM-CSF and GM-CSF-R mRNA in human fetal organs at 8 and 16 wk postconception, and cell-specific protein expression was localized in tissues by immunohistochemistry. GM-CSF was also measured by ELISA in paired samples of spinal fluid and plasma. GM-CSF mRNA and/or protein were detected in lung macrophages, spleen, adrenal cortex, placenta, and CNS including neurons and astrocytes. GM-CSF was detected by ELISA in 10 of the 39 cerebrospinal fluid samples tested. GM-CSF-R mRNA expression was present in all organs tested. Immunoreactivity for GM-CSF-R in most organs was limited to macrophages, but, brain, neurons and glial cells showed immunoreactivity. We conclude that GM-CSF is produced in lung, spleen, adrenal, placenta, and neural tissues during human fetal development and that GM-CSF-responsive cells include macrophages, neurons, and glial cells.