We studied the influence of cyclosporin-A (Cy-A) on resistance of mice to systemic infection with Candida albicans. Cy-A clearly inhibited resistance to C. albicans. The effect was dose-dependent and time and route of administration of the drug were important. This immunodepressive effect was due, at least in part, to an impairment of polymorphonuclear leucocyte (PMNL) candidacidal activity, as demonstrated in vitro by a reduction of phagocytic and cytotoxic activity and in vivo by protection when PMNL from untreated mice were transferred into cyclophosphamide-treated hosts challenged with C. albicans. The decreased activity of PMNL could be partly restored by adoptive transfer of normal T-lymphocytes into Cy-A-treated mice, as well as by exposure of PMNL to gamma-interferon (IFN-gamma) in vitro.