OBJECTIVE: Besides the functions of histones in the nucleus of the cells, there is growing evidence that histones have many other extra-cellular or extra-nuclear functions, such as stabilizing axonemal microtubule of sea urchin sperm flagella. This microtule assembly function of the histone is similar to that of taxol, which has an effect of controlling joint inflammation. In this study, a possible suppressive effect of histones on a mouse collagen-induced arthritis(CIA) model was investigated. METHODS: A DBA/1 mouse were injected intradermally with emulsified chicken type II collagen. Three weeks after immunization, histone H1 was injected intraperitoneally twice a week. Clinical incidences of arthritis and arthritis index were measured. Anti-collagen antibodies and stimulation index of the splenocytes of mice were measured. IL-10 and TNF-alpha in the supernatants of the cultured splenocytes were measured by ELISA. IL-10 and TNF-alpha in the supernatants of the cultured U937 cells stimulated with histone H1 were measured by ELISA. mRNA expression of IL-10 and TNF-alpha in the U937 cells stimulated with histone H1 were observed. RESULTS: Histone H1 appears to be an effective suppressor of CIA in mice. When delivered intravenously, this suppressive effect of histone H1 was most effective compared to intraperitoneal or intradermal injections. The anti-collagen antibody level of the histone H1 treated group was significantly lower than that of the control group. A remarkable increase in the level of IL-10 was observed from the cultured supernatant of the splenocytes treated with histone H1. Also, an increase of IL-10 level was observed from the cultured supernatant of the U937 cells treated with histone H1. CONCLUSION: According to these results, histone H1 appears to have a suppressive effect on CIA. The mechanism of the suppressive effect of histone may be a stimulation of IL-10 production.