The mechanism by which the expression of adenosine deaminase (ADA, EC 3.5.4.4) is regulated in murine tissues was analyzed. Elevated levels of the specific activity of this enzyme appeared to correlate directly with steady state levels of ADA mRNA. Transcriptional studies using nuclear run-on experiments revealed a pronounced asymmetric distribution of nascent transcripts across the ADA genome. The ability to detect nascent transcripts downstream of the promoter proximal region varied among tissues and correlated with tissue levels of ADA mRNA and enzymatic activity. These results indicate that processes affecting the elongation of nascent transcripts into completed primary transcripts play a role in tissue-specific expression of ADA.