Using synthetic oligonucleotide probes, we have isolated chicken cDNA clones for the intermediate filament protein desmin. We show that the gene for this protein probably exists as a single copy in the haploid chicken genome and is transcribed into one mature mRNA species of approximately equal to 2.4 kilobases. Expression of this mRNA is tissue-specific, as it is present in high abundance in smooth and skeletal muscle but is absent from erythrocytes, spinal cord, and lens cells. A 10- to 20-fold increase in desmin mRNA is observed in myogenic cells upon fusion, which suggests that the level of expression of the desmin gene and the accumulation of desmin filaments during muscle differentiation is regulated at the transcriptional and/or posttranscriptional level but not at the translational level. Hybridization studies and nucleotide sequence comparison of the cDNAs specific for desmin and for other intermediate filament subunits reveal a region that is highly conserved (80%) among different members of the intermediate filament protein gene superfamily, with the exception of the chicken vimentin gene; this gene appears to be less homologous to the genes for the other chicken intermediate filament subunits than the mammalian vimentin gene is to the genes for other mammalian intermediate filament proteins and to the chicken desmin gene.