Retinoids affect many biological processes such as cell proliferation, differentiation and morphogenesis, but their effects on arthritic patients and animal models of arthritis are controversial. We tested the effect of a novel synthetic retinoic acid, Am-80 (4-[(5,6,7,8-tetrahydro-5,5,8,8,-tetramethyl-2-naphthalenyl) carbamoyl] benzoic acid), on type-II collagen (CII)-induced arthritis (CIA) in rats. Am-80 markedly suppressed the incidence of arthritis, hindpaw swelling and bone destruction. In contrast, 13-cis-retinoic acid (13-cis-RA) hardly inhibited these CIA symptoms. Moreover, Am-80, but not 13-cis-RA, strongly reduced the serum level of anti-CII antibody and differentially affected the levels of immunoglobulin (Ig) subclasses in vivo: IgG1 and IgG2a levels were decreased, while IgA level was increased without any change in the IgM level. These findings indicate that Am-80 may be one of the lead retinoic acids of a new class of anti-inflammatory agents.