In Drosophila, a large group of structural genes exhibit coordinate regulation, not because they function in a common developmental pathway but because they happen to reside on the X chromosome. These genes are subjected to the regulatory mechanism of dosage compensation which insures that their phenotypic products are identical in the sex with one and in the sex with two X chromosomes. This equilization of gene products is achieved by regulating the level of transcription of both X chromosomes in females and of the single X chromosome in males. We report here that, reasoning that sex-specific lethal mutations may represent lesions in the processes controlling the transcription of X-linked loci, we sought and recovered several male-specific lethal mutations and noted that they affect the levels of X-linked enzyme activities in crude extracts of homozygous male larvae. Autoradiographic monitoring of RNA synthesis in larval polytene chromosomes of males homozygous for one of these mutations, mlets, reveals a significant reduction in the rate of X chromosome transcription.