Mercury, an occupational and environmental contaminant, is a well-recognized health hazard. The thymus is a target for inorganic mercury (Hg2+); thymic function is impaired in Hg2+ intoxication and is partially restored by simultaneous L-arginine supplementation. The nitric oxide (NO)-nitric oxide synthase (NOS) pathway and metallothioneins (MTs) were studied to investigate the role of L-arginine in thymic function restoration after mercury exposure. Mice received a higher and a lower dose of inorganic mercury, with and without L-arginine supplementation. Saline-treated mice were used as controls. Thymus weight and thymulin were measured as indices of thymic function. Mice treated with Hg2+ alone displayed an accumulation of metal in the thymus, reduced NOS activity, a lower plasma nitrite plus nitrate concentration and an increased MTs expression compared with control mice. L-arginine supplementation was associated with lower Hg2+ concentrations in the organ and partial preservation of other measures. Reduced accumulation of Hg2+ in mice dosed with L-arginine was probably related to greater NO production and NO-MTs interactions.