Arginase‐1 (Arg1) catalyzes the final step in the urea cycle to convert arginine to ornithine + urea. In the rarest of the urea cycle disorders, genetic deficiency of Arg1 results in hyperargininemia with occasional bouts of hyperammonemia, eventually leading to neurological problems and failure to thrive. Arg1 deficient mice die at two weeks of age. In order to circumvent the early mortality we generated an inducible knockout model by crossing “floxed” Arg1 deficient mice (JAX strain C57BL/6‐Arg1tm1Pmu/J) with Cre‐ER‐T2 mice (JAX strain B6.129‐Gt(ROSA)26Sortm1(cre/ERT2)Tyj/J). Arg1‐Cre mice were indistinguishable from control mice. However, when treated with 4‐OH‐tamoxifen for 2 days at birth by intragastric administration, or for 5 consecutive days with i.p. tamoxifen at 4, 8, or 12 weeks (n=4–8) all mice died within 12–14 days or reached humane endpoints. DNA analysis confirmed the deletion of exons 7 and 8 and Western blot analysis showed loss of Arg1 expression in mouse embryo fibroblasts and liver hepatocytes derived from tamoxifen‐treated Arg1‐Cre mice. Hyperammonemia was evident in the crisis period 7–12 days after tamoxifen administration prior to gait and imbalance problems that presented clinically at the end stage. These mice should be a useful model to study the mechanisms of neurological deficits resulting from Arg1 deficiency in aged mice provided that the hyperammonemia can be controlled.