Collagen-induced arthritis (CIA) is an experimental autoimmune disease that can be elicited in susceptible strains of rodents (rat and mouse) and nonhuman primates by immunization with type II collagen (CII), the major constituent protein of articular cartilage. Because of the important similarities between CIA and rheumatoid arthritis, this experimental model of autoimmune arthritis has been the subject of extensive investigation in several laboratories. Protocols for CIA are described in this unit for both the mouse model and the rat model. In addition, protocols are included for the purification of CII from bovine articular joints and chicken sternums, for the purification of collagen a1(II) chains, and for the purification of fragments of these chains following cyanogen bromide (CNBr) digestion. The preparation of CII is a time-consuming procedure but is usually required because of the scarcity and expense of commercial sources of purified native CII. In addition, support protocols are provided for assessing the severity of inflammation following CIA and for measuring B and T cell responses to CII.