.The sex difference in the metabolism of certain mRNAs in the murine submaxillary gland (SMG) prompted us to determine whether androgens regulate the expression of any of the four isoforms of AUF1, proteins that bind differentially to AU-rich RNA. We found that cytosol from female SMGs contains two major isoforms (p45 and p40), whereas cytosol from male SMGs contains a prominent p37 and a weaker p42. Injecting female mice with testosterone decreases p45 levels by 81% after 7 days (P < 0.05, n = 4), whereas p42 and p37 increase 74 and 449% at 7 days (P < 0.05, n = 4, for both). Orchiectomy, conversely, decreases p37 levels in the male SMG by 91% (P < 0.006) while increasing p45 5-fold and p40 2.5-fold (P < 0.05, n = 5 for both). Both male and female kidney cytosol contains a prominent p37 and a faint band of ~42 kDa, but neither shows a significant change when circulating androgen levels are altered. Dihydrotestosterone (DHT) changes the pattern of AUF1 isoforms in female SMG cytosol more rapidly than does testosterone. Nuclear extracts from female SMG contain predominantly p45, and DHT decreases its level slightly (35%, P < 0.05 at 24 h). Polysomal extracts from female SMG contain p45 and p42, and DHT increases p45 levels 58% (P < 0.02, n = 6) at 24 h. In certain nonreproductive tissues, androgens may differentially regulate AUF1 isoform levels to modulate the metabolism of AU-rich mRNAs posttranscriptionally.