The renin-angiotensin system plays a role in many physiological systems, as proven by the phenotype of angiotensin-converting enzyme (ACE) knockout mice. We have used homologous recombination to create novel lines of mice with limited and unusual expression patterns of ACE. These mice show that, as long as an animal can regulate renin, they can tolerate both unusual patterns and reduced expression of ACE. We have also created mice in which one of the two ACE catalytic sites is nonfunctional. These new lines of mice give great insight into the function of the renin-angiotensin system in blood pressure control, response to stress, hematopoiesis, and reproduction.