Intraperitoneal injection is a common technique that safely delivers a substance into the peritoneal cavity but can induce high stress in animals. The authors have developed a new method for administering intraperitoneal injections in mice, with the goal of causing less stress during handling and injection. Here, they compare their novel technique with a conventional technique in three experiments. In the first experiment, the authors administered intraperitoneal injections of contrast medium using either technique and then used micro-computed tomography to evaluate the placement and retention of the medium. In the second and third experiments, the authors administered intraperitoneal injections or control treatments, then sampled blood to determine circulating concentrations of stress-related hormones. Imaging showed that both the novel and the conventional techniques properly delivered a contrast medium into the peritoneal cavity. The novel technique was also associated with lower concentrations of stress-related hormones than was the conventional technique. These results indicate that this novel technique might be beneficial to investigators that use intraperitoneal injections with mice.