Heart transplantation has in recent months become a clinical fact. Its experimental development reaches back over 60 years, and has been augmented, particularly in the field of immunosuppression, by knowledge gained from studies of kidney transplantation. Research workers were faced with a number of questions. Would a denervated heart function effectively, if at all? How would it respond to various pharmacological agents? Would the pattern of “rejection” be similar to that in other organs? How could immunological rejection of the heart be assessed clinically? What would be the most effective form of immunosuppression? And, finally, would the findings gained from experimental work on dogs be applicable to man? Today most of these and other questions have been answered, at least in part, and this paper traces the many stages of progress in this field, from the pioneering work of Carrel and Guthrie in 1905 to the first attempts at cardiac transplantation in man by Hardy and his associates in 1964 and by Barnard and his colleagues in 1967. © 1968, British Medical Journal Publishing Group. All rights reserved.