We report a null mutation in the human ciliary neurotrophic factor gene (CNTF). The mutated allele shows a G to A transition producing a new splice acceptor site and the resulting mRNA species codes for an aberrant protein. Analysis of tissue samples and transfection of CNTF minigenes into cultured cells demonstrates that the mutated allele expresses only the mutated mRNA species. In 391 Japanese people tested, 61.9% were normal homozygotes, 35.8% heterozygotes and 2.3% mutant homozygotes. The distribution of the three genotypes is similar in healthy and neurological disease subjects, indicating that human CNTF deficiency is not causally related to neurological diseases.