Antibodies to native bovine type II collagen may be important in initiating arthritis in rats immunized with this antigen. The cross-reactivity of these antibodies with native rat type II collagen was higher in rats that developed arthritis than in those that did not. Depletion of serum C3 levels by cobra venom factor delayed the onset of arthritis until C3 levels were returning to normal; therefore, complement may be involved in initiation of the arthritis, and this arthritis may be an example of an immune complex--mediated disease.