Considerable research has been conducted on the development, safety, and efficacy of a recombinant vaccinia-rabies glycoprotein (V-RG) oral vaccine for wildlife in the United States. Starting in 1990, field trials of V-RG assessed safety and efficacy with raccoons as the original primary target species. Prior to licensing, over a 5-year period the effects of oral V-RG vaccine on both target and non-target warm-blooded vertebrates were tested in various states. Working in academia and government, I was involved in the initial trials on Parramore Island Virginia in 1990, State Game Lands 13 in Sullivan County Pennsylvania in 1991, Cape May Peninsula, New Jersey from 1992 to 1994, and the Cape Cod, Massachusetts isthmus along the canal in 1994. Gradually, these different locations reflected a shift in the focus of comparative field testing, from an isolated island, to a remote area on the mainland, to an area with a sporadic, seasonal human population, to a moderate human habitation, respectively. Sites were chosen based upon multiple criteria, but most importantly associated with relative raccoon abundance, the interface with domestic animals, and the opportunity for engagement with human populations. I also participated in later V-RG field studies in Pinellas County, Florida, Albany, New York, and in many other activities in the assessment of this unique biologic in the prevention and control of raccoon rabies. The findings and conclusions in this report are those of the author and do not necessarily represent the official position of the Centers for Disease Control and Prevention.