In 1955–57, in the course of a study initiated by Charles Hume and the Universities Federation for Animal Welfare, Rex Burch and I conceived of the Three Rs of humane experimental technique — replacement, reduction and refinement. Except for the foundation, in 1969, and the early work, of FRAME, the next two decades saw little development of the Three Rs, and widespread scepticism about the possibilities of replacement, especially in activity and toxicity testing. In the 1980s and early 1990s, advances in tissue culture technique led to spectacular progress in fundamental pharmacology and toxicology. There have also been important recent advances in aspects of refinement discussed in our book published in 1959, notably in anaesthesia and analgesia, and in the application of ethology. However, there has been less progress in reduction, except for one ingenious new statistical technique for reducing numbers of animals used for testing vaccines. Developments we scarcely touched on in 1959 include the application of the Three Rs to the production and testing of vaccines, the education of experimenters in laboratory animal science (both of these developments pioneered in The Netherlands), and the replacement of animals in teaching by the use of computers and audiovisual displays. A priority for the future is the application of the Three Rs to work with primates. New uses for experimental animals continue to arise, but, after recent successes, we can now have considerable confidence in the progress of humane experimental technique.