Formosanin-C, a diosgenin saponin, was isolated from a perennial herb, Parisformosana Hayata (Liliaceae) which has been used as a folk remedy for snake bite and as an anti-inflammatory or antineoplastic agent. Its effect on the development of S-antigen-induced experimental autoimmune uveitis (EAU) in guinea pigs was studied. Guinea pigs treated with formosanin-C (1.5 mg/kg/2 days and 0.5 mg/kg/2 days) were compared with untreated guinea pigs in regard to the development of EAU, lymphocytic proliferative responses, and anti-S-antigen serum antibodies. The higher dosage of formosanin-C (1.5 mg/kg) obviously delayed the onset of EAU. Treatment of this drug, 1.5 mg/kg and 0.5 mg/kg doses, significantly inhibited the specific lymphocytic response of lymph node and spleen cells to S-antigen. On the contrary, treatment in 1.5 mg/kg dose significantly increased the response of lymph node and spleen cells to the polyclonal T cell mitogen, phytohemagglutinin (PHA). Treatment with formosanin-C in both the 1.5 mg/kg and 0.5 mg/kg doses had a minimal effect on the lymphocytic response of lymph node to concanavalin-A (ConA), while a noticeable suppressive effect on the response of spleen cells to ConA was observed in the 1.5 mg/kg dose. This agent in 1.5 mg/kg and 0.5 mg/kg doses significantly inhibited the anti-S-antigen antibody production by days 14 and 18 postimmunization. This study suggests that formosanin-C, an immunomodulator, may offer a new approach to modulate the development of EAU.