We investigated effects of IL-4, dexamethasone (DXM), and the combination of IL-4 and DXM, low- or high-dose, on collagen-induced arthritis (CIA) in DBA/1 mice and correlated severity of arthritis with changes in IL-10 and IFN-gamma. Compared with control mice, mice treated with IL-4 had increased IL-10 with the same degree of arthritis, whereas mice treated with high-dose DXM had decreased IL-10 and increased IFN-gamma production with less severe arthritis. Mice treated with low-dose DXM showed the absence of IL-10 and increased IFN-gamma production with a trend toward the resolution of arthritis. Mice treated with IL-4 and low-dose DXM had neither IL-10 nor IFN-gamma production but revealed less severe arthritis, compared with mice treated with low-dose DXM alone. These results suggest that the beneficial effects of high-dose DXM and the combination of IL-4 and DXM on CIA are independent of IL-10 and IFN-gamma.