Because the term "alternatives" was never completely defined in any Federal policy or regulation, until recently, it led to considerable confusion among investigators. Often, research personnel interpreted the term to mean alternatives to the use of animals in general, which it does not. Recently, the Office of Technology Assessment clarified the issue by referring to the concept of alternatives as presented in Russell and Burch, The Principles of Humane Experimental Technique (1959). In their book, the authors present three encompassing categories which have been termed the "three Rs", replacement, reduction, and refinement. It is these three concepts that are now required by USDA policy to be considered in the search for alternative methodologies. The full text of the book is available on-line. Below is a description and some examples of applying the "three Rs" to animal research.