Cyclosporin, a naturally occuring fungal metabolite, also inhibits T-cell activation and cell-mediated immunity. The drug becomes active only when complexed to its intracellular receptor cyclophilin, and it inhibits early calcium-dependent events, especially the activation of several cytokine gene. Its major effect is the inhibition of IL-2 production and the CD4 proliferation responses. Cyclosporin has been extremely useful in the control of transplant rejection and is also used in several autoimmune diseases such as psoriasis and severe rheumathoid arthritis. However, long-term use has demonstrated severe toxicity such as nephrotoxicity and hepatotoxicity and particularly lymphoma induction.