A murine model of oral candidiasis was used to show that nitric oxide (NO) is involved in host resistance to infection with Candida albicans in infection‐‘resistant’ BALB/c and infection‐‘prone’ DBA/2 mice. Following infection, increased NO production was detected in saliva. Postinfection samples of saliva inhibited the growth of yeast in vitro. Treatment with N^G‐monomethyl‐l‐arginine (MMLA), an inhibitor of NO synthesis, led to reduced NO production, which correlated with an increase in C. albicans growth. Reduction in NO production following MMLA treatment correlated with an abrogation of interleukin‐4 (IL‐4), but not interferon‐γ (IFN‐γ), mRNA gene expression in regional lymph node cells. Down‐regulation of IL‐4 production was accompanied with an increase in IFN‐γ production in infection‐‘prone’ DBA/2 mice. There was a functional relationship between IL‐4 and NO production in that mice treated with anti‐IL‐4 monoclonal antibody showed a marked inhibition of NO production in saliva and in culture of cervical lymph node cells stimulated with C. albicans antigen. The results support previous conclusions that IL‐4 is associated with resistance to oral candidiasis and suggest that NO is involved in controlling colonization of the oral mucosal surface with C. albicans.