The finding of Helicobacter hepaticus infection in our acetylcholinesterase (AChE) knockout mouse colony led to a search for a treatment. One-hundred percent of AChE +/+, 100% of AChE +/-, and 35% of AChE -/- mice tested positive. The lower infection rate in AChE -/- mice, who are routinely weaned on day 15, suggested that early weaning might be an effective eradication strategy. The AChE +/+ and +/- mice were weaned on days 13, 14, 15, or 16. Litters were placed in sterile, heated, isolator cages. Animals were fed liquid Ensure Fiber and 11% fat pelleted diet. Feces were tested for the presence of H. hepaticus by use of DNA amplification. Litters weaned on days 14, 15, or 16 had a high rate (68, 63, and 100%, respectively), whereas litters weaned on day 13 had a lower (8%) rate of infection. Uninfected animals have remained free of H. hepaticus through day 120. Pups weaned on day 13 lost body weight, beginning on day 14, but recovered by day 16. It is concluded that the non-coprophagic behavior of AChE -/- mice accounts for a low infection rate and that the combination of early weaning, routine testing, and culling provide an effective method for eradication of H. hepaticus.