To determine the source of angiotensinogen excreted in urine, urine angiotensinogen was measured in male and female rats during growth. Angiotensinogen in 24-hr urine, measured by direct radioimmunoassay with antibody against rat angiotensinogen, increased fourfold in males between the ages of 5 and 7 weeks, whereas no significant changes were observed in females or castrated males. Plasma levels of angiotensinogen, in contrast, showed no significant differences between these groups at any age. Castration of adult males caused a significant reduction of urinary angiotensinogen after 4 weeks. Consecutive s.c. administration of 17 alpha-methyltestosterone for 3 weeks in castrated males resulted in a threefold increase in the urinary excretion of angiotensinogen, as well as a twofold increase in the renal expression of angiotensinogen messenger RNA (mRNA). Renal levels of angiotensinogen mRNA in intact adult males were about threefold higher than those in females and castrated males, whereas there were no significant differences in hepatic angiotensinogen mRNA between these animals. These results suggest that the sexual differences in the urinary excretion of angiotensinogen are primarily due to the androgen-dependent dimorphic expression of angiotensinogen mRNA in the kidney; thus, levels of angiotensinogen in urine might reflect intrarenal production.