The cytotoxic drug 6-mercaptopurine (6-MR b-thiopurine) and the closely related immunosuppressive agent azathioprine (6-(1-methyl-4-nitro-5-irnidazolylthio) purine) act as purine antagonists (Fig. 1). They interfere with biochemical processes involving endogenous purines, which are essential components of DNA, RNA, and certain co-enzymes. Both mercaptopurine and azathioprine have cytotoxic and immunosuppressive properties that are variously due to the inhibition of the synthesis of proteins, DNA, and RNA, with additional effects attributable to the reactive thiot group. Mercaptopurine was initially evaluated for the treatment of leukaemia in the early 1950s [Burchenal et al. 1953]. Its potential value as an immunosuppressive was demonstrated by Schwartz et al.(1958), who showed that in laboratory animals injected with an antigen, treatment with mercaptopurine prevented the development of an antibody response. Azathioprine, a" masked" form of mercaptopurine, was found to be a more potent immunosuppressive agent in dogs [Calne et al. 1962], and this led to its introduction in clinical transplantation in the early 1960s [Murray et al. 1963]. Despite the widespread use of these compounds for over three decades precise details of their molecular basis of action in man are lacking.