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Replacement is one of the obvious alternatives. It is the use of non-animal techniques or the use of animals lower on the phylogenetic scale in the conduct of the research. Using Russell & Burch's concepts of "fidelity" and "discrimination" the replacement alternative emphasizes the use of low fidelity models (models that do not share a high proportion of characteristics with the human model) that have high discrimination (a model that shares ONE characteristic of the human model) for the process under investigation. Examples include use of cell culture or tissue culture, use of microbes for measurement of carcinogenic potential of compounds, use of invertebrates as has been done in the past (lobster and squid for nerve studies, limulus for visual electrophysiology). Some replacement alternatives may require the investigator to acquire new skills or invest in new materials and equipment. In many cases production of antibodies is performed in a live animal. While if properly done, this procedure causes little, if any, pain or distress in the animal subject, a model which produces a larger quantity of antibody is the fertilized chicken egg. Use of this procedure is more technically difficult and somewhat more expensive but should be considered when antibody production is required. Related to such a procedure is using mechanical biochemical systems for the production of hybridomas.

The replacement alternative for some procedures must often wait for the development or validation of new technologies. The Johns Hopkins Center for Alternatives to Animal Testing is actively pursuing the development and validation of such alternatives.

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