Androgen-regulated changes in the abundance of two mRNAs in mouse kidney have been studied with the aid of a cDNA clone. The clone was isolated from a library prepared using poly(A+) RNA from kidneys of androgen-induced mice and is designated MAK-I. Unique DNA sequence from MAK-I hybridizes to multiple RNAs which are approximately 1600 and 2200 nucleotides long, and Southern blot analysis of genomic DNA suggests that there is a single gene from which the RNAs are transcribed. When the MAK RNAs are isolated by hybrid selection and translated in a cell-free system, one polypeptide of 42,000 daltons is obtained. The transcripts, in combination, comprise approximately 0.2% of poly(A+) RNA in the kidneys of male mice. Following treatment with testosterone, this level increases 3-fold. The uninduced level of MAK mRNA in female kidneys is half of that exhibited by males and is increased 8-fold by testosterone. The mRNAs are also present and their abundance is hormonally controlled in the liver. Levels of MAK RNA detected in submaxillary gland, heart, brain, muscle, and testes are unaffected by testosterone treatment. Differences in the relative amounts of the different sized mRNAs are observed for several tissues. In addition, brain and muscle contain an intermediate sized mRNA instead of the smaller one seen in other tissues. Functional androgen receptor is required for expression of MAK RNA in kidney as shown by reduced levels in Tfm mice. Hormones produced by or controlled by the pituitary gland do not appear to be involved in the regulation of MAK RNA levels.