Oral administration of CII has been shown to prevent the induction of CIA in DBA/1J mice. Recently, it was also reported that oral administration of a peptide derived from CII had both preventive and therapeutic effects. No study to date has assessed the effect of intranasal immunization with CII on CIA. In this study, we have examined prophylactic and therapeutic effects of oral and intranasal immunization with bovine CH. When DBA/1J mice were immunized with CII over a low dose regimen by either oral or intranasal routes before the induction of CIA, the incidence of CIA was reduced and the onset of CIA was delayed for several weeks. Further, both CIIspecific DTK and antibody responses were reduced by 20-40 %. Although DTH responses specific to CII did not change significantly in either low or high dose regimen, the onset of CIA was delayed for several weeks in mice which received low doses of CII by intranasal immunization after CIA had been induced. On the other hand, high intranasal doses increased the incidence of CIA. Intranasal immunization with a low dose of CII had not only prophylactic but also therapeutic effects on CIA.