The effects of adjuvant-induced arthritis in the rat on serum protein alterations were investigated in a longitudinal study. Injection of an emulsion of the Wax D fraction of the tubercle bacillus in oil elicited pronounced elevations in the α1-globulin, α2-globulin, and seromucoid fractions, and the total serum glycoprotein within 24 h. During the acute stage of the disease, significant increases were observed in protein-bound hexose, and in the fibrinogen, seromucoid, α1-, α2-, and β-globulin fractions. A new protein, α2-AP (acute phase) globulin, appeared in the serum concomitant with decreased levels of total protein, albumin, and γ-globulin. Remission was characterized by a reversal of the above changes. Spontaneous renewal of the arthritic symptoms caused comparable but less marked serum changes similar to those observed in the various clinical phases of rheumatic disease in man. It was concluded that although the serum changes parallel to a certain extent the degree of pathologic activity, they are not specific, and reflect a common systemic response to inflammation.