We previously showed the rat thymus contains and secretes active renin. However, the cellular location of the thymic renin-angiotensin system (RAS) is unknown. To more easily study the thymic RAS we used the hypertensive transgenic (mRen-2)27 rat which overexpresses renin and angiotensin in extra-renal tissues. Comparisons were made with normotensive Sprague Dawley (SD) rats. All rats exhibited intense immunolabeling for renin protein and angiotensin in macrophages and thymic epithelial cells, however renin prosequence was not detected. In each rat strain, thymic renin was predominately active and highest in Ren-2 rats (Ren-2, 22.6+/-4.2, SD 0.8+/-0.1 mGoldblatt Units/g, mean+/-SEM). Renin mRNA was identified in Ren-2 and SD rat thymus by RT-PCR. Thymic angiotensin II concentrations/wet weight in Ren-2 (20.1+/-1.1 fmol/g) and SD (15.8+/-2.3 fmol/g) rats were similar to plasma. In conclusion, macrophages and epithelial cells are the source of active renin in the rat thymus. The thymic RAS may have actions systemically and may also influence local processes such as blood flow and cell growth.