Mucosal Candida albicans infection in immunocompromised individuals being treated with recently advanced drugs can progress to systemic disease. One such medication applied in patients with rheumatoid arthritis is leflunomide. The object of the present study was to investigate the effect of leflunomide on a model of gastrointestinal (g.i.) C. albicans infection induced in naïve or arthritic mice and on the host resistance to systemic re-infection. Newborn mice were orally inoculated with 1 x 10(5) colony forming units (CFU) of C. albicans and at age of 5 weeks they were treated with 5 mg/kg or 20 mg/kg of leflunomide for 10 consecutive days. Both doses elevated the yeast colonization of the stomach, without the dissemination into the internal organs. This was in parallel with the enhanced delayed type hypersensitivity (DTH) reaction to the yeast. Contrary to that, leflunomide caused a shift to Th2 reactivity by prevalence of IL-4 to IFN-gamma and a suppression of anti-Candida antibody synthesis by a higher dose. It might be supposed that infection increased autoimmune response in arthritic mice, according to stimulated DTH reaction to collagen. The administration of leflunomide during the simultaneous development of infection and arthritis diminished anti-Candida and anti-collagen antibody synthesis compared to untreated infected arthritic mice. The improved survival of arthritic infected animals against severe systemic re-infection was not changed after administration of leflunomide to re-infected arthritic mice. We can conclude that although leflunomide influenced cytokine secretion and suppressed anti-Candida antibody production it neither provokes a progression from gastrointestinal to systemic C. albicans infection nor increases the susceptibility to severe C. albicans re-infection of arthritic mice.