Ethylcysteine showed a prophylactic effect on collagen-induced arthritis in rats at 100 mg/kg, p.o., and the effect continued even after stopping the administration. However, it was not dose-dependent. D-penicillamine showed no effect under the same condition. Ethylcysteine tended to inhibit collagen-induced arthritis when it was administered therapeutically at 300 mg/kg, p.o. Moreover, it had little effect on the acute inflammatory and type I allergy models such as carrageenin induced edema, 48 hr homologous PCA, and 6 hr and 24 hr Evans blue-carrageenin pleurisy in rats. In the in vitro assay, ethylcysteine had the following effects: inactivation of the rheumatoid factor, the acceleration of the denaturation of human gamma-globulin and the inhibition of bone alkaline phosphatase. The effect were as potent as those of D-penicillamine. As to the results, the mode of action of ethylcysteine is the same as that of D-penicillamine in terms of the biochemical properties. However, ethylcysteine showed an inhibitory effect on collagen-induced arthritis which was not demonstrated with D-penicillamine, so this drug may have a clinically anti-rheumatic action.