Amplification of the N-myc gene has been reported in a number of tumour types including neuroblastoma, retinoblastoma and small cell lung carcinoma. Two amplified human N-myc genes have been sequenced. To determine whether any sequence changes accompany gene amplification and hence to define more precisely the mechanism of activation of the N-myc gene, we have sequenced a germ-line N-myc gene. This sequence differs from the amplified gene sequences by only a single base substitution, which may represent a polymorphic site. This comparison indicates that neither changes in gene structure nor nucleotide sequence accompany gene amplification. Analyses of four small cell lung carcinoma cell lines with amplification of the N-myc gene using restriction endonucleases and Northern blotting reveal no structural aberrations of the majority of the gene copies, substantiating the concept that amplification of the N-myc gene results in high levels of structurally normal N-myc mRNA.