"Replacement" is the substitution for a "higher order" species with a "lower order" species or by non-living tissue culture (or a non-living system like a computer model). The rationale for "replacement" is that use or lower order and non-living tissues does not present the same or same level of distress in the animal, or in the case of euthanasia the same level of ethical concern. "Replacement" is the strongest response to the ethical problems encountered in scientific animal use.
Ultimately, the concept of "replacement" is stated in the Nuremberg Code (on human subjects of research), as follows: "3. The experiment should be so designed and based on the results of animal experimentation and a knowledge of the natural history of the disease or other problem under study that the anticipated results will justify the performance of the experiment." In other words, "replacement" begins with substitution of lower animals for the human beings, who are the nominal beneficiaries of the research. Likewise, we endeavor to substitute systems such as tissue culture or computer modeling for lower animals whenever possible.