The immune response of rats to type II collagen was modified by pretreating the rats with levamisole, hydrocortisone, or cyclophosphamide. Rats were observed for the development of collagen-induced arthritis and were bled serially for the determination of antibody levels to type II collagen. Levamisole had a slight but not significant potentiating effect with arthritis developing earlier, whereas hydrocortisone and cyclophosphamide significantly depressed the incidence of arthritis; cyclophosphamide also delayed its onset. Antibody levels measured by radioimmunoassay paralleled the clinical course of arthritis.