Neurotrophic factors are essential neurone survival promoting molecules that are often secreted and that bind to neuronal cell surface receptors. Glial cell line-derived neurotrophic factor, GDNF, is a potent neurotrophic factor that promotes the survival of dopaminergic neurones in cultures including embryonic neuronal cultures. We have mapped the gene encoding GDNF by two independent methods: using a cell hybrid panel and by fluorescent in situ hybridisation. We find GDNF lies on the short arm of human chromosome 5, at 5p13.1-p13.3 ability to promote dopamine uptake in midbrain cultures. The protein was partially sequenced and a rat GDNF cDNA was isolated by screening a B49 cDNA library with an oligonucleotide probe designed from the amino-terminus of the rat protein. Human GDNF sequences were isolated by screening a human genomic library with a portion of the rat GDNF cDNA (Lin et al. 1993). We wished to localise the GDNF gene in the human genome and determine its proximity to possible sites of mutation, particularly phenotypes affecting neuronal function.