The anti-arthritic effects of cytogenin (8-hydroxy-3-hydroxymethyl-6- methoxyisocoumarin) on type II collagen-induced arthritis in DBA/1J mice and adjuvant arthritis in Lewis rats were examined. Prophylactic treatment with cytogenin (30, 100 mg/kg) had a potent inhibitory effect on type II collagen-induced arthritis. Prophylactic or therapeutic treatment with cytogenin (10, 30 and 100 mg/kg) also had a potent inhibitory effect on adjuvant arthritis. In contrast to nonsteroidal anti-inflammatory drugs (NSAIDs), cytogenin (10, 30 and 100 mg/kg) had neither an anti-inflammatory effect on carrageenan-induced paw oedema in rats nor an analgesic effect on acetic acid-induced writhing in mice. These results suggest that the mode of the anti-arthritic action of cytogenin is different from that of NSAIDs and that cytogenin may become a useful drug for the treatment of rheumatoid arthritis.