GDNF expression was examined immunocytochemically in developing human fetal brains obtained from aborted fetuses ranging from 7 to 39 weeks in gestational age. At 7-8 weeks, strong immunoreactivity was noted within radial glial processes, glia limitans and choroid plexus of the telencephalic vesicle. By 10 weeks, ependymal cells, primitive matrix cells and early developing cortical plate neurons showed positive staining. By 15-16 weeks, migrating neurons in the subventricular and intermediate zones and in the cortical plate were strongly positive for GDNF. The glia limitans of the cerebral cortex and subependymal astrocytes remained positive at this time. As fetal age increased, GDNF expression shifted to neurons and glial cells in the deeper structures of the brain. The most prominent GDNF staining was observed in the cytoplasm and dendrites of Purkinje cells of the cerebellum by 25 weeks and thereafter. Pyramidal neurons of the CA1 region and granule cells of the dentate fascia of the hippocampus, neurons of the entorhinal cortex, and scattered neurons within the brain stem, medulla and spinal cord all showed strong GDNF staining by 25-35 weeks. Widespread GDNF expression in neuronal and non-neuronal cells with distinct developmental shifts suggests that GDNF may play a critical role in the survival, differentiation and maintenance of neurons at different stages of development in the developing human fetal brain.