Neurobromatosis type 1 (NF1) is one of the commonest genetic disorders in humans. The gene for NF1 was cloned in 1990. The protein encoded by the gene (neurofibromin) has extensive sequence homology with GTPase-activating protein (GAP). Despite screening the whole coding region of the gene for large and medium size rearrangements and approximately 40% of the coding region of the gene for small alterations, only 45 germ-line mutations have been reported in more than 500 unrelated patients. Of these, 25 mutations involve small changes in the gene, of which 17 (68%) result in the formation of an inappropriate stop codon. A "hot spot" for mutations has not been identified. The high mutation rate at this locus and the general difficulty in identifying mutations are discussed. A complete understanding of the structure and function of the NF1 gene awaits further detailed studies of both naturally occurring and in vitro-generated mutations.