The renin-angiotensin system (RAS) has been hypothesized to play a central role in mediating the cardiovascular changes observed in both normal and hypertensive pregnancies. From serial studies in both humans and animals, circulating levels of all components of the RAS (renin, angiotensinogen, angiotensin II) have consistently been shown to be elevated 2-3 fold during pregnancy. Despite the considerable evidence that the RAS is potentially important in cardiovascular control, there is a paucity of information concerning regulation of the genes of the RAS during pregnancy. Information on the regulation of the human RAS is especially lacking. Six transgenic female mice carrying the human renin gene underwent timed pregnancies with C57BL/6J male mice. At 16-18 days of gestation (term = 20 days), the mice were sacrificed along with age-matched non-pregnant female littermates (N=6). Kidneys, myometrium (separate from chorioamniotic membranes), and placentas were removed for mRNA expression. Human and mouse renin mRNA expression was measured by RNase protection assay. High level of both human and mouse renin mRNA was detected in all placentas analyzed. Human and mouse renin mRNA expression was found in both pregnant and non-pregnant myometrium samples. The level of expression in the uterus of non-pregnant female mice exhibited significant variation among samples. Uterine expression of human renin mRNA, however, appeared significantly elevated during pregnancy. Surprisingly, both human and endogenous renin expression within the kidney remained unchanged in pregnant samples (vs non-pregnant controls). These results suggest the possibility of a tissue renin-angiotensin system within the uteroplacental unit which is active during pregnancy and may have important maternal or fetal physiological consequences.