The transcriptional activity of renin genes in the mouse kidney and submandibular gland (SMG) was examined by measurement of renin messenger RNA (mRNA) (nanograms per g tissue) and compared with renin activity (micro-moles angiotensin I per h/g tissue). In control adult mice renin mRNA and renin activity (in parentheses) were 1.8 ± 0.24 (11 ± 1.1) in male kidney, 3.6 ± 0.66 (18 ± 2.8) in female kidney, 230 ± 34 (903 ± 59) in male SMG, and 31 ± 6 (188 ± 47) in female SMG (mean ± se, n = 6). The ratio of renin mRNA among these four tissues was similar to that of renin activity (1:2:100:17, respectively). Although the values in male kidney were one one-hundredth those in SMG, 1000 to 10000 times more SMG cells are involved per gram of tissue so that, per renin-synthesizing cell, kidney values would be 10 to 100 times SMG values. Expression of renin gene(s) in a renal juxtaglo-merular cell may thus be higher than in a SMG granular duct cell. Values in adult male SMG were a consequence of a 40-fold rise at puberty, were decreased to 16% (±3.8) by castration, but were not significantly influenced by treatment with testosterone, T₄, propylthiouracil, sodium depletion, or spironolactone. Renin mRNA in adult female SMG was 18-fold higher than juvenile values, was increased 10-fold (±1.6) by testosterone (to adult male levels) and 5.5-fold (±0.81) by T₄ (P < 0.005), but was decreased to 42% (±29) of normal by propylthiouracil (P < 0.05). Propylthiouracil caused a small but significant decrease in testosterone-treated female values. In the kidney renin mRNA was increased 3.0-fold (±0.30) by captopril, 2.3-fold (±0.23) by a low sodium diet, and 1.7-fold (±0.13) by spironolactone after 1 week, whereas T₄, testosterone, or propylthiouracil had little or no effect. Sialoadenectomy increased renin mRNA and renin in male but not in female kidney, suggesting that a SMG factor, possibly renin, may have a role in suppression of renin synthesis in male kidney. In conclusion, measurement of renin mRNA suggests that testosterone regulates renin gene expression by a direct effect in male mouse SMG, whereas in the female regulation is by thyroid hormone. In the kidney conditions which increase renin content are accompanied by parallel (5-fold higher) increases in renin mRNA, suggesting enhanced expression of renin gene(s) in renal juxtaglomerular cells in chronic low sodium states. (Endocrinology117: 872–878, 1985)