The isoxazol derivative leflunomide (HWA 486) is a novel immunomodulating drug, representing a new small molecule class of substances which are structurally unrelated to previously described immunomodulatory/immunosuppressive compounds. It has been shown to be efficacious in animal models of autoimmune diseases (eg adjuvant arthritis, MRL/lpr disease and chronic graft versus host disease [1] and allo or xeno transplantation rejection (skin, kidney and pancreatic islet cell)[1-3]. The data from phase II clinical studies indicate that the compound is safe and efficacious in the treatment of rheumatoid arthritis [1]. Leflunomide's main metabolite A77 1726 is a potent antiproliferative compound in-vitro [1]. Previous experiments indicated that leflunomide inhibits activation of human lymphocyte through preventing Gl-phase transition of the cell cycle, determined by interleukin 2 and transferrin receptor expression after PHA or anti-CD3 stimulation. In addition, the substance leads to the accumulation of proliferating tumour cell lines in the early S-Phase of the cell cycle [4]. Further, washing the cells free of leflunomide enabled them to resume proliferation, indicating that the substance's antiproliferative effect is non-cytotoxic and fully reversible. In order to elucidate the antiproliferative activity of leflunomide in more detail, we conducted experiments to: 1. render cells resistant to leflunomide and 2. determine if intermediates of purine and pyrimidine biosynthesis were able to reverse this effect.