The purpose of this study was to evaluate the impact of angiotensinogen gene (Agt) deficiency on reproductive fitness in a rodent model. Mice with 0 (Agt^−/−), 1 (Agt^−/ ), and 2 (Agt ^/ ) copies of Agt were bred according to the following schemes: 1) Agt^−/− × Agt^−/−, 2) Agt^−/ × Agt^−/ , 3) Agt ^/ × Agt ^/ , and 4) Agt ^/ ♀ × Agt^−/ ♂. There were 4 breeding pairs per scheme. Breedings were time mated. Mice and litters were weighed daily. Southern blotting was used for genotyping. We found that Agt^−/− breeding pairs had fewer litters (2 [range 1–2] vs. 4 [range 3–5]; P = 0.01), fewer pups per litter (4 [range 1–7] vs. 6 [range 1–10]; P = 0.006), and longer interpregnancy intervals (43 days [range 31–44] vs. 35.5 days [range 22–58]; P = 0.04) compared to wild-type controls. The ratio of postcoital plugs to subsequent litters was 4.0 and 1.2 for Agt^−/− and Agt ^/ breedings, respectively (P = 0.03). Median maternal weights during all trimesters of pregnancy were significantly lower for Agt-deficient mice compared to wild-type controls. Among Agt^−/ × Agt^−/ breedings, the proportions of Agt ^/ (n = 17), Agt^−/ (n = 38), and Agt^−/− (n = 4) offspring differed significantly from the expected 1:2:1 Mendelian inheritance pattern (P = 0.03). Neonatal survival among the offspring derived from the Agt^−/− × Agt^−/− breeding scheme was significantly reduced (P = 0.001). We conclude that Agt deficiency is associated with an in utero lethal effect, decreased fertility, and impaired neonatal survival.