Cyclosporine A (CsA) is a potent inhibitor of cell-mediated immunity. Controlled trials in Crohn's disease with low-dose CsA (≪ 5 mg/kg/day) did not show efficacy for either chronically active inflammatory disease or for maintenance of remission. Uncontrolled trials of high-dose CsA (≫ 5 mg/kg/day oral or 4 mg/kg/day i.v.) suggest efficacy for both inflammatory and fistulous Crohn's disease. Both uncontrolled trials and one controlled study suggest that high-dose CsA is efficacious for severe ulcerative colitis (UC). A controlled trial of low-dose CsA enemas for left-sided UC did not show efficacy. There is a significant theoretical risk of irreversible CsA-associated nephropathy following treatment of inflammatory bowel disease (IBD) with high-dose CsA. Severe infectious complications may also occur rarely. It appears that CsA must be used at relatively high (and potentially toxic) dosages to achieve efficacy in IBD. Future studies should evaluate the efficacy and safety of the short-term use of high-dose CsA as “rescue therapy” in severe inflammatory Crohn's disease and UC, as well as in fistulous Crohn's disease.