The acute-phase reactant, C-reactive protein, is a good index of disease activity in patients with rheumatoid arthritis. We examined the murine acute-phase reactant, serum amyloid P, as an index of disease in type II collagen-induced arthritis in 3 mouse strains. The onset of type II collagen-induced arthritis, which is characterized by paw swelling, is associated with a significant, but transient, elevation of serum amyloid P. Anticollagen antibody titers are not temporally associated with the onset of disease. Although murine type II collagen arthritis fails to show the chronic acute-phase reactant elevation that is characteristic of arthritis in humans, the transient elevation of the acute-phase reactant is a reliable indicator of the onset of disease.